Amiocordin - instructions for use, dose, side effects, contraindications

Amiodarone refers to III class antiarrhythmic drugs (class of inhibitors repolarization) and has a unique mechanism of antiarrhythmic action, as well as the properties of antiarrhythmics III class (potassium channel blockade), it has antiarrhythmic effects I class (blockade of sodium channels), antiarrhythmics IV class (calcium channel blockade) and noncompetitive beta-adrenergic blocking action.

In addition to antiarrhythmic action, he has an antianginal, coroparasshaving, alpha and beta-adrenergic blocking effects.

Antiarrhythmic properties:

- an increase in the duration of the third phase of the action potential of cardiomyocytes, mainly due to the blocking of the ion current in the potassium channels (the effect of the antiarrhythmic agent III class by 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 atrioventricularpnode;

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

Other effects:

- decrease in oxygen consumption by myocardium due to a moderate decrease in 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 transformation triiodothyronine (T₃) in thyroxine (T₄) (Blockade of 5-thyroxine deiodinase) and blocking capture these hormones cardiomyocytes and hepatocytes, which leads to a weakening effect of thyroid stimulating hormone pas myocardium;

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

Pharmacokinetics:

With intravenous administration of amiodarone, its activity reaches a maximum after 15 minutes and disappears approximately 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 has a large volume of distribution and can accumulate in almost all tissues, especially in adipose tissue and in addition to it - in the liver, lungs, spleen and cornea.

The connection with plasma proteins is 95% (62% with albumin, 33.5% with beta-lipoproteins).

Amiodarone is metabolized in the liver by 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 desethylamiodarone under conditions in vitro have the ability to inhibit isoenzymes CYP1Al, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8.

Amiodarone and desethylamiodarone also demonstrated the ability to inhibit certain transporters, such as P-glycoprotein (P-gp) and carrier of organic cations (PKK2). In conditions in vivo interaction of amiodarone with substrates of isozymes CYP3A4, CYP2C9, CYP2D6 and P-gp.

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 excreted by hemodialysis.

Indications:

- Cessation 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) (risk of "stopping" the sinus node).

- Atrioventricular block II-III degree 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, Amiocordin^® intravenously is possible only in specialized departments under the guise of a temporary pacemaker (pacemaker).

- Simultaneous use with drugs that can lengthen the interval QT and cause the development of paroxysmal tachycardia,including ventricular tachycardia of the "pirouette" type (see section "Interaction with other drugs"):

antiarrhythmic drugs: IA class (quinidine, hydroquinidine, disopyramide procainamide), antiarrhythmic drugs of the III class (dopstylide, ibutilide, brethil tosylate), sotalol;
other (non-antiarrhythmic) drugs, such as beprideal, wincamine, some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide, cisapride, ficicylic antidepressants, macrolide antibiotics (in particular erythromycin with intravenous administration, spiramycin), azoles, antimalarial drugs (quinine, chloroquine, mefloquine, halofaptrine), pentamidine for parenteral administration, dipemannyl methyl sulfate, misolastine, astemizole, terfenadine, fluoroquinolones.

- Congenital or acquired lengthening interval QT.

- Severe decrease in arterial pressure, collapse, cardiogenic shock.

- Hypokalemia, hypomagnesemia.

- Thyroid dysfunction (hypothyroidism, hyperthyroidism).

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

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

- Age to 18 years (efficiency and safety ns 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 Amyocordin^® when performing cardiac recovery in case of cardiac arrest caused by ventricular fibrillation resistant to defibrillation.

Carefully:

With arterial hypotension, uncompensated or severe chronic heart failure (III-IV functional class by classification NYHA), hepatic insufficiency, bronchial asthma, severe respiratory failure, 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 fetal thyroid, amiodarone contraindicated during pregnancy, except in special cases when the expected benefit exceeds the risk (in case of life-threatening ventricular arrhythmias).

Breastfeeding period

Amiodarone is excreted in breast milk in significant amounts, so it is contraindicated during breastfeeding (it is necessary to cancel the drug or stop breastfeeding).

Dosing and Administration:

Amiocordin®, a solution for intravenous administration, is intended for use in those cases where rapid attainment of antiarrhythmic affect is required, or if oral administration is not possible.

Except for urgent clinical situations, the drug should be used only in a hospital in the intensive care unit under the constant control of the electrocardiogram (ECG) and blood pressure (BP)!

When administered intravenously, Amyocordin® should not be mixed with other drugs. Do not inject other drugs into the same line of the infusion system as the Amyocordin® preparation. Apply only in diluted form. To dilute the drug Amiocordin ® should be used only 5% solution of dextrose (glucose). Amyocordin® should be administered through the central venous catheter to avoid reactions at the site of administration, except for cases of cardiac retention in ventricular fibrillation resistant to defibrillation, when, in the absence of central venous access, it is possible to administer the drug to the peripheral veins (usually the largest peripheral vein with maximum blood flow).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 recovery 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 with the help of an 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.

The 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 Amiocordin®, an intravenous solution, it is recommended to switch to a permanent intravenous drip introduction of the drug.

Supportive 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 the infusion, you should begin a gradual transition to taking Amyocordin® 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 administration is usually not recommended because of hemodynamic risk (a sharp decrease in blood pressure, collapse) is possible, an infusion introduction of the drug is preferable, if possible.

Intravenous jet infusion should be performed only in urgent cases with ineffectiveness of other types of treatment and only in intensive care unit under constant monitoring of ECG, AD.

The dose is 5 mg / kg body weight. With the exception of cases of cardiac revascularization with ventricular fibrillation resistant to defibrillation, intravenous spray administration of Amyocordin^® should be held for at least 3 minutes.

Repeated administration of Amyocordin^® should not be performed earlier than 15 minutes after the first injection, even if the contents of only one ampoule were introduced at the first injection (the possibility of developing an irreversible collapse).

If there is a need to continue the introduction of Amyocordin®, it should be administered as an infusion.

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

Intravenous Injection (see section "Special instructions")

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

If the fibrillation does not stop, then an additional intravenous jet of Amyocordin^® in a dose of 150 mg (or 2.5 mg / kg).

Elderly patients

In the treatment of elderly patients, the lowest loading and maintenance doses of Amyocordin^®.

Side effects:

The incidence of adverse events was determined in accordance with the World Health Organization (WHO) classification: 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 (it is not possible to determine the frequency from the available data).

Violations of the blood and lymphatic system:

frequency unknown: neutropenia, agranulocytosis.

Violations from the heart and blood vessels:

often: a bradycardia, usually mild, a decrease in blood pressure, usually mild and transient. In case of overdose or too rapid administration of the drug, there were cases of pronounced decrease in blood pressure or collapse;

very rare: arrhythmogenic effect (occurrence of new rhythm disturbances or weighting of existing rhythm disturbances, in some cases with subsequent cardiac arrest), severe bradycardia, stopping of 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;

frequency unknown: ventricular tachycardia of the pirouette type (see section "Interaction with other drugs", subsection "Pharmacodynamic interaction", section "Special instructions").

Disorders from the endocrine system:

very rarely: syndrome of inadequate secretion of antidiuretic hormone;

frequency unknown: hyperthyroidism.

Disorders from the digestive system:

very rarely: nausea;

frequency unknown: pancreatitis / acute pancreatitis.

General disorders and disorders at the site of administration:

often: reactions at the injection site, such as pain, erythema, edema, necrosis, extravasation, infiltration, inflammation, compaction, thrombophlebitis, phlebitis, cellulitis, infection, skin pigmentation changes.

Disturbances from the liver and bile ducts:

very rarely: an isolated increase in the activity of "hepatic" transaminases in the serum, usually moderate (exceeding the upper limit of the norm (VGN) from 1.5 to 3 times), observed at the beginning of treatment. Activity of "hepatic" transaminases can return to normal values with decreasing dose or even spontaneously, acute liver damage with increased activity of "liver" transaminases and / or jaundice, including development of hepatic insufficiency, sometimes fatal (see section "Special instructions"). .

Immune system disorders:

Very rarely: anaphylactic shock;

frequency unknown: angioedema (Quincke's edema).

Disorders from the metabolism and nutrition:

frequency unknown: decreased appetite.

Disturbances from musculoskeletal and connective tissue:

frequency unknown: pain in the lumbar and lumbosacral spine.

Disturbances from the nervous system:

very rarely: benign intracranial hypertension (pseudotumor of the brain), headache;

frequency unknown: Parkinsonism.

Disorders of the psyche:

frequency unknown: state of confusion / delirium, hallucinations.

Violation of the genitals and mammary gland:

frequency is unknown: decreased libido.

Disturbances from the respiratory system, chest and mediastinal organs:

very rarely: interstitial pneumonitis (see section "Special instructions"), severe respiratory complications (acute adult respiratory distress syndrome), sometimes fatal (see "Special instructions", "Interaction with other drugs"), bronchospasm and / or apnea in patients with severe respiratory failure, especially in patients with bronchial asthma.

Disturbances from the skin and subcutaneous tissues:

very rarely: increased sweating;

frequency unknown: eczema, urticaria, severe skin reactions, sometimes fatal,including toxic epidermal necrolysis / Stevens-Johnson syndrome, bullous dermatitis, drug reaction with eosinophilia and systemic symptoms.

Overdose:

There is no information about an overdose of amiodarone for intravenous use.

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 tachycardia such as pirouette, circulatory disorders and liver function, marked decrease in LD are described.

Treatment should be symptomatic (with bradycardia - the use of beta-adrenostimulyatorov or the installation of a pacemaker, with ventricular tachycardia such as "pirouette" - intravenous injection of magnesium salts, pacing pacemaking).

Neither amiodarone, nor its metabolites are removed during hemodialysis. There is no specific antidote.

Interaction:

Pharmacodynamic interaction

Medicines that can cause a bi-directional ventricular tachycardia such as "pirouette" or increase the duration of the interval QT

Medicines that can cause ventricular tachycardia such as "pirouette"

Combination therapy with drugs that can cause ventricular pirouette tachycardia is contraindicated, as this increases the risk of potentially legal ventricular pirouette tachycardia. These include:

antiarrhythmic drugs: 1A class (quinidine, hydroquinidine, disopyramide, procainamide), sotalol;
other (non-antiarrhythmic) drugs, such as beprideal, wincamine, some neuroleptics: phenothiazines (chlorpromazine, ciammazin, levomenromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, nimozide, tricyclic antidepressants, cisapride, macrolide antibiotics (erythromycin with intravenous administration, spiramycin), azoles, antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine), pentamidine for parenteral administration, dipemannyl methyl sulfate, misolastine, astemizole, terfenadine.

Drugs that can increase the duration of the interval QT

Simultaneous reception of amiodarone with drugs that can increase the duration of the interval QT, should be based on a careful assessment for each patient of the relationship between expected benefit and potential risk (the possibility of an increased risk of ventricular pirouette tachycardia), with such combinations it is necessary to constantly monitor the patient's ECG (to determine the lengthening of the interval QT), as well as the content of potassium and magnesium in the blood. In patients receiving amiodarone, fluoroquinolones should be avoided, including moxifloxacin.

Medicines that reduce heart rate, or cause violations of automatism or conduction

Combination therapy with these drugs is not recommended.

Beta-adrenoblockers, blockers of "slow" calcium channels, which cut heart rate (verapamil, diltiazem), can cause violations of automatism (the development of excessive bradycardia) and conduction.

Medicinal products, capable of causing hypokalemia

Uncommon combinations:

with laxatives, stimulating intestinal motility, which can cause hypokalemia, increasing the risk of developing a ventricular pirouette tachycardia. Simultaneously with amiodarone, laxatives of other groups should be used.

Combinations requiring caution when used:

with diuretics causing hypokalemia (in monotherapy or in combination with other drugs);
with systemic corticosteroids (glucocorticosteroids, mineralocorticosteroids), tetracosactide;
with amphotericin B (intravenous administration).

It is necessary to prevent the development of hypokalemia, and in the case of the emergence to restore to normal values the content of potassium in the blood, to control the content of electrolytes in the blood and the ECG (for possible lengthening of the interval QT), and in the case of ventricular tachycardia, the typhoid "pirouette" should not be used with antiarrhythmic drugs (ventricular pacing, intravenous injection of magnesium salts) should be started.

Medicines for general anesthesia

The possibility of developing the following serious complications in patients taking amiodarone, while performing general anesthesia: bradycardia (resistant to atropine), lowering blood pressure, conduction disorders, reducing cardiac output.

There were very rare cases of severe complications from the respiratory system, sometimes with a fatal outcome (acute respiratory distress syndrome of adults), which developed immediately after surgery, the occurrence of which is associated with interaction with high concentrations of oxygen.

Medicines 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 isoenzymes CYP1AI, CYP1A2, CYP3A4. CYP2C9, CYP2D6 and P-gp and can increase the systemic exposure of medicines that are their substrates. Due to the prolonged period of hemi-exposure of amiodarone, this interaction can be observed even a few months after discontinuation of its administration.

Medicines that are substrates P-gp

Amiodarone is an inhibitor P-gp. It is expected that its simultaneous reception with drugs that are substrates 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 a digox with amiodarone, an increase in the concentration of digoxin in the blood plasma is possible (due to a decrease in its clearance). Therefore, with simultaneous use of digoxin 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

Care should be taken when using amiodarone and 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.

Medicines that are the substrates of the isoenzyme CYP2C9

Amiodarone increases the concentration in the blood of drugs,which are substrates of isoenzyme CYP2C9, such as warfarin or phenytoin by inhibiting the isoenzyme CYP2C9.

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 monitor prothrombin time by determining the INR (international normalized ratio) and correcting the doses of indirect anticoagulants, either during treatment with amiodarone or after stopping it.

Phenytoin

With the simultaneous use of phenytoin with amiodarone, the development of an overdose of phenytoin may occur, which may lead to the appearance of neurological symptoms. Clinical monitoring and reduction of the dose of phenytoin is necessary at the first signs of overdose, it is desirable to determine the concentration of phenytoin in the blood plasma.

Medicines that are the substrates of the isoenzyme CYP2D6

Flecainide

Amiodarone increases the plasma concentration of flecainide by inhibiting the isoenzyme CYP2D6, in connection with which correction of doses of flecainide is required.

Medicines that are the substrates of the isoenzyme CYP3A4

With the simultaneous use of amiodarone, an inhibitor of isoenzyme CYP3A4, these drugs 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. Such medicines are listed below.

Cyclosporin

Simultaneous use of cyclosporine with amiodarone may increase the concentration of cyclosporine in the blood plasma, dose adjustment 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 HMG-CoA reductase (statins) (simvastatin, atorvastatin and lovastatin)

Increased risk of muscle toxicity (rhabdomyolysis) with simultaneous use of amiodarone and statins metabolized by isoenzyme CYP3A4. We recommend the use of statins that are not metabolized by isoenzyme CYP3A4.

Other drugs metabolized by the isoenzyme CYP3A4: lidocaine (risk of developing 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 drug that is a substrate of isoenzymes CYP2D6 and CYP3A4

Dextromethorphan

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

Clopidogrel

Clopidogrel, which 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.

Influence of other drugs or amiodarone

Inhibitor inhibitors CYP3A4 and CYP2C8 may have the potential to inhibit the metabolism of amiodarone, increase its concentration in the blood and. accordingly, the risk of increasing its pharmacodynamic and side effects.

It is recommended to avoid the intake of inhibitors of the isoenzyme CYP3A4 (for example, grapefruit juice and some medicines, such as cimetidine and HIV protease inhibitors (v.h. indinavir)) during treatment with amiodarone. HIV protease inhibitors, when used simultaneously with amiodarone, can increase the concentration of amiodarone in the blood.

Inductors of isoenzyme CYP3A4

Rifampicin

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

Preparations of St. John's Wort

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

Special instructions:

Intravenous jet administration of Amyocordin® is usually not recommended due to hemodynamic risks (development of pronounced decrease in blood pressure, vascular collapse), intravenous drip introduction of the drug is preferable.

Intravenous fluid administration of Amyocordin® should be performed only in the intensive care unit with constant monitoring of the ECG (due to the possibility of bradycardia and arrhythmogenic effect) and blood pressure (in connection with the possibility of reducing blood pressure).

In order to avoid the occurrence of reactions at the injection site (see Fig.section "Side effect"), the drug Amiocordin®, solution for intravenous administration, it is recommended to enter through a central venous catheter. Only in the case of cardiac retention in case of cardiac arrest caused by ventricular fibrillation resistant to defibrillation, in the absence of central venous access (absence of an established central venous catheter) Amyocordin® preparation, intravenous solution, can be injected into a large peripheral vein with maximum blood flow. If it is necessary to continue treatment with Amiocordin® after cardiac recovery, Amyocordin® should be administered intravenously via a central venous catheter under constant monitoring of blood pressure and ECG.

The drug Amiocordin® 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 Amyocordin® preparation (see the "Application and Dosage" section).

Reactions from the heart

There were reports of new rhythm disturbances or weighting of already existing rhythm disturbances, sometimes with a legal outcome.It is very important, but difficult, to make a differential diagnosis between insufficient effectiveness of the drug and its arrhythmogenic effect, whether or not combined with an aggravation of the severity of the cardiovascular pathology.

When using Amyocordin®, the arrhythmogenic effect was reported significantly less frequently than with other antiarrhythmic drugs and was usually observed in the presence of factors that increased the duration of the QT interval, such as interaction with other drugs and / or impaired electrolyte content in the blood ( see the sections "Side effect" and "Interaction with other drugs"). Despite the ability of Amyocordin® to increase the duration of the QT interval, it showed low activity with respect to provoking ventricular pirouette tachycardia.

Pulmonary disorders

The appearance of dyspnea or dry cough may be associated with pulmonary toxicity, in particular with the development of interstitial pneumonitis. In very rare cases, the development of interstitial pneumonitis was observed after intravenous administration of Amyocordin®.If suspected development of interstitial pneumonitis in patients who have severe dyspnoea, both isolated and in combination with worsening of the general condition (fatigue, weight loss, fever), an X-ray examination of the lungs should be performed. Amiocordin® should be reevaluated because, with an early discontinuation of the drug, interstitial pneumonitis is usually reversible (clinical symptoms are usually resolved within 3-4 weeks, followed by a slower improvement in the radiographic pattern and lung function for several months). Consideration should be given to the treatment of glucocorticosteroids.

In addition, in patients who received Amyocordin®, in very rare cases, usually immediately after surgery, a serious respiratory complication (acute adult respiratory distress syndrome) was observed, sometimes with a fatal outcome; it is possible to link its development with interaction with high concentrations of oxygen (see section "Side effect").

Disorders from the side of the liver

It is recommended to carefully monitor the functional "liver" tests (monitoring the activity of "liver" transaminases) before starting the drug Amiocordin^® and regularly during drug treatment. During the first 24 hours after intravenous administration of Amiocordin^®, acute liver damage (including hepatocellular insufficiency or liver failure, sometimes with a legal outcome) and chronic liver damage can develop. Therefore, with an increase in the activity of "hepatic" transaminases, which is 3 times higher than VGN, the dose of Amyocordin^® should reduce or stop receiving it.

Clinical and laboratory signs of chronic liver failure with Amyocordin® oral administration can be minimally expressed (hepatomegaly, increased transaminase activity 5 times higher than UGN) and reversible after drug withdrawal, however, deaths have been reported.

Severe bullous reactions

Treatment with Amiocordin® should be stopped immediately if symptoms and manifestations of life-threatening or even fatal reactions appear in the form of Stevens-Johnson syndrome,toxic epidermal necrolysis, namely: the emergence of progressive skin rash, often with the formation of blisters, or the appearance of damage to the mucous membranes.

Drug Interactions

It is not recommended simultaneous use of Amyocordin® with the following drugs: beta-adrenoblockers, blockers of "slow" calcium channels, which cut heart rate (verapamil, diltiazem), laxatives, stimulating peristalsis of the intestine, which can cause hypokalemia.

Hypokalemia

Hypokalemia should be corrected before starting Amyocordin®.

Children

In children, the safety and efficacy of Amyocordin® has not been studied. Ampoules of Amyocordin®, a solution for intravenous administration, contain gasoline alcohol. It was reported about the development in newborns of a sharp choking with a fatal outcome after intravenous administration of solutions containing gasoline alcohol. Symptoms of this complication are acute development of choking, lowering of blood pressure, bradycardia and collapse.

General and local anesthesia

Before surgery, an anesthesiologist should be informed that the patient was given Amyocordin®. Treatment with Amiocordin® may increase the hemodynamic risk inherent in local or general anesthesia (especially in terms of cardiac arrhythmia, conduction slowdown, and reduced heart contractility).

Thyroid dysfunction

Amiocordin® can cause thyroid dysfunction, especially in patients with thyroid dysfunction in their own or family history. Therefore, in the case of switching from Amyocordin® intravenously to Amiocordin®, 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, TSH concentration in the blood serum should be determined (using a supersensitive TSH assay). The drug Amiocordin® contains in its composition iodine and therefore can disrupt the absorption of radioactive iodine,which can distort the results of a radioisotope study of the thyroid gland, but its use does not affect the reliability of the determination of the concentration of T₃, T₄ and thyroid-stimulating hormone in the 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 precautionary measure for patients with paroxysms of severe rhythm disturbances during the treatment with Amiocordin®, it is advisable to refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous administration, 50 mg / ml.

Packaging:

3 ml of the drug are placed in ampoules of neutral glass (type I). The ampoule has a colored dot on the fault site and a color coding ring.

5 ampoules are placed in a PVC / aluminum foil blister. 1 blister is placed in a pack of cardboard along with instructions for use.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 of the year.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N011617 / 02

Date of registration:18.01.2010 / 10.11.2015

Expiration Date:Unlimited

Date of cancellation:2017-09-26

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp26.09.2017

Illustrated instructions

Instructions

Amiocordin® (Amiokordin®)