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

Amiodarone belongs to class III of antiarrhythmic agents (class of inhibitors of repolarization) and has a unique mechanism of antiarrhythmic action, g. in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (sodium channel blockade), class IV antiarrhythmics (calcium channel blockade), and uncompetitive beta-adrenergic blocking action.

In addition to antiarrhythmic action, he has angianginal, coronary dilatation, alpha and beta-adrenergic blocking effects.

The severity of the action of amiodarone reaches a maximum after 15 minutes after its intravenous administration and stops after approximately 4 hours.

Antiarrhythmic properties are due to:

- Increase in the duration of the third phase of the action potential of cardiomyocytes (mainly due to blocking of the ion current in the potassium channels - the effect of the III class antiarrhythmic drug according to Williams classification);

- Decreased automatism of the sinus node, leading to a decrease in the heart rate (heart rate);

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

- Slowing of intracardiac (sinoatrial, atrial and atrioventricular - AV) conductivity. This action is more pronounced with tachycardia. Significant influence on intraventricular conduction amiodarone does not render;

- An increase in the duration of the refractory period and a decrease in the excitability of myocardiocytes of the atria and ventricles, as well as an increase in the duration of the refractory period AV node;

- Slowing of the speed and duration of the refractory period in additional beams of the atrioventricular conduction.

Other effects of amiodarone:

- Decrease in oxygen consumption by myocardium due to a moderate decrease in total peripheral vascular resistance (OPSS) and heart rate, as well as myocardial contractility;

- 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 (due to a decrease in OPSS and afterload);

- Effect 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 myocardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones;

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

Pharmacokinetics:

The concentration in the blood of the parenterally administered amiodarone decreases very rapidly due to the intensive distribution of the drug. Amiodarone has a large volume distribution and can accumulate in almost all tissues, as well as in the liver, lungs, spleen and cornea.

The connection with plasma proteins is 95% (62% with albumin, 33% with beta-lipoproteins).

Amiodarone is metabolized in the liver with the participation of isoenzymes CYP3A4 and CYP2C8. Its main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the basic compound.

Amiodarone and desethylamiodarone in vitro have the ability to inhibit isoenzymes CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and desethylamiodarone are also capable of inhibiting some transporters (P-glycoprotein-P-gp) and carrier of organic cations (PKK2). In vivo interaction of amiodarone with substrates of isozymes CYP3A4, CYP2C9, CYP2D6 and P-gp.

It is brought out very slowly, mainly with bile through the intestine. Amiodarone and its metabolites are determined in blood plasma for 9 months after discontinuation of treatment. Amiodarone and its metabolites are not dialyzed.

Indications:

Cessation of paroxysmal tachyarrhythmias:

- attacks of ventricular paroxysmal tachycardia;

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

Cessation of paroxysmal and permanent forms of atrial fibrillation (atrial fibrillation) and atrial flutter.

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

Contraindications:

All of the following contraindications do not apply to the use of the drug during cardiac revival with cardiac arrest caused by ventricular fibrillation resistant to defibrillation.

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

- Hypersensitivity to iodine, amiodarone or excipients of the drug.

- Syndrome of weakness of the sinus node (sinus bradycardia, sinoatrial block), except for cases of using an artificial pacemaker (the danger of "stopping" the sinus node).

- AV blockade II-III degree in the absence of a permanent artificial pacemaker.

- Violations of intraventricular conduction (two- and three-beam blockades) in the absence of a permanent artificial pacemaker (pacemaker). With such conductivity disorders, the use of the drug Amiodarone 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 tachycardias, including polymorphic 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 (dofetilid, ibutilid, brethil tosylate); sotalol; beprideil;

· 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; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine; astemizole, terfenadine; fluoroquinolones.

- Congenital or acquired lengthening interval QT.

- Severe decrease in blood pressure (BP), cardiogenic shock, collapse.

- Hypokalemia, hypomagnesemia.

- Dysfunction of the thyroid gland (hypothyroidism, hyperthyroidism).

- Pregnancy, the period of breastfeeding (see para.section "Application during pregnancy and during breast-feeding").

- Age under 18 years (efficiency and safety not established).

Carefully:

Arterial hypotension, cardiomyopathy, severe decompilation of heart failure (III-IV Functional class according to the classification of the New York Heart Association (NYHA)), severe respiratory failure due to interstitial lung diseases, hepatic insufficiency, bronchial asthma, elderly age (high risk of severe bradycardia), AV blockade of the 1st degree.

Pregnancy and lactation:

Pregnancy

Currently available clinical information is not sufficient to determine whether it is possible or impossible to develop developmental defects in the embryo when using amiodarone in the first trimester of pregnancy.

Since the fetal thyroid begins to bind iodine only from the 14th week of pregnancy, then it is not expected to affect her amiodarone in the case of its earlier use. Excess iodine during the use of the drug after this period may lead to the appearance of laboratory symptoms of hypothyroidism in newborns or even to the formation of a clinically significant goiter in it.

In view of the possible effects on the thyroid of the fetus amiodarone contraindicated during pregnancy, except when the expected benefit of its use by a pregnant woman exceeds the risk in the fetus (with life-threatening ventricular arrhythmias).

Breastfeeding period

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

Dosing and Administration:

Amiodarone (concentrate for the preparation of a solution for intravenous administration) is intended for use in those cases when rapid antiarrhythmic effect is required or its administration is not possible.

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

The drug is used only in diluted form. To dilute the drug Amiodarone Only 5% dextrose (glucose) solution should be used. Do not add other drugs to the infusion solution!

In connection with the features of the dosage form of the drug, It is not possible to administer an infusion solution with a concentration of less than 0.6 mg / ml (2 ampoules in 500 ml of a 5% solution of dextrose (glucose)).

To avoid local reactions, the drug Amiodarone should be administered through a central venous catheter, except in cases of cardiac recovery in ventricular fibrillation, resistant to defibrillation, when it is possible to inject the drug into large peripheral veins - in the absence of central venous access (see section "Special instructions").

Severe disturbances of heart rhythm, in cases, when it is impossible to take the drug inside (except for cases of cardiac recovery in case of cardiac arrest, induced fibrillation of the ventricles, resistant to defibrillation)

Intravenous drip introduction through the central venous catheter

Usually the loading dose is 5 mg / kg of body weight, administered whenever possible with the infusomat for 0.3-2 hours. The 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, so if it is necessary to continue treatment with the drug Amiodarone it is recommended to switch to a permanent intravenous drip introduction of the drug.

Supportive treatment: 10-20 mg / kg / day of body weight (average 600-800 mg / day, maximum dose 1200 mg / day) for several days. From the first day of infusion, you should begin a gradual transition to taking the drug inside (3 tablets of 200 mg per day). The dose can be increased to 4 or even up to 5 tablets per day.

Intravenous Injection

Intravenous fluid administration is usually not recommended because of the risk of hemodynamic complications (there may be a sharp drop in blood pressure and collapse).

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 and blood pressure.

The dose is 5 mg / kg body weight. With the exception of cases of cardiac retention in ventricular fibrillation resistant to defibrillation, intravenous spray administration of the drug Amiodarone must be carried out for at least 3 minutes. Repeated administration of the drug should not be performed earlier than 15 minutes after the first injections, even if the contents of only one ampoule were initially introduced (the possibility of developing an irreversible collapse).

If there is a need to continue the administration of the drug Amiodarone, 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")

It is recommended to use a central venous catheter, in case of its absence, the drug Amiodarone must be injected into the largest peripheral vein.

The initial dose is 300 mg (5 mg / kg body weight), after dilution in 20 ml of 5% dextrose (glucose) solution to a concentration of 15 mg / ml.

If fibrillation does not stop, an additional intravenous jet injection of the drug Amiodarone in a dose of 150 mg (or 2.5 mg / kg body weight) to a concentration of 7.5 mg / ml.

Do not mix in the same syringe with other drugs!

Side effects:

The incidence of adverse events was determined in accordance with the classification of the World Health Organization (WHO): very often (≥10%), often (≥1%, <10%); infrequently (≥0.1%, <1%); rarely (≥0.01%, <0.1%) and very rarely, including individual reports (<0.01%), the frequency is unknown (according to available data, it is not possible to determine the frequency).

Violations of the blood and lymphatic system

Frequency unknown

- Neutropenia, agranulocytosis.

Disorders from the cardiovascular system

Often

- Bradycardia, usually mild.

- Reduced blood pressure, usually mild and transient. When an overdose or too rapid introduction of the drug, there were cases of pronounced reduction in blood pressure or collapse.

Rarely

- Arrhythmogenic action (occurrence of new rhythm disturbances, or aggravation of existing rhythm disturbances, in some cases with subsequent cardiac arrest).

- Severe bradycardia, 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.

Frequency unknown

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

Disorders from the endocrine system

Rarely

- Syndrome of inadequate secretion of antidiuretic hormone (SNSAG).

Frequency unknown

- Hyperthyroidism.

Disorders from the digestive system

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, densification, thrombophlebitis, phlebitis, cellulitis, infection, skin pigmentation changes.

Disturbances from the liver and bile ducts

Rarely

- Isolated increase in the activity of "hepatic" transaminases in the blood serum, usually mild (exceeding the upper limit of the norm from 1.5 to 3 times), observed at the beginning of treatment. The 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

Rarely

- Anaphylactic shock.

Frequency unknown

- Angioedema (edema of Quincke).

Disturbances from musculoskeletal and connective tissue

Frequency unknown

- Pain in the lumbar and lumbosacral spine.

Disturbances from the nervous system

Rarely

- Benign intracranial hypertension (pseudotumor of the brain), headache.

Disorders of the psyche

Frequency unknown

- The state of confusion / delirium, hallucinations.

Violation of the genitals and mammary gland

Frequency unknown

- Decreased libido.

Disturbance from the respiratory system, organs of the chest and mediastinum

Rarely

- Interstitial pneumonitis or fibrosis, sometimes fatal (see section "Special instructions").

- Severe respiratory complications (acute respiratory distress syndrome of adults), sometimes fatal (see section "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

Rarely

- Increased sweating.

Frequency unknown

- Eczema, hives, severe skin reactions, sometimes fatal,including toxic epidermal necrolysis, Stevens-Johnson syndrome, bullous dermatitis; drug reaction with eosinophilia and systemic symptoms.

Disturbances on the part of the organ of sight

Frequency unknown

- Neuropathy of the optic nerve / neuritis, which can progress to blindness.

Overdose:Information on an overdose of amiodarone (concentrate for the preparation of a solution for intravenous administration) is not available. There are several cases of acute overdose of amiodarone taken internally, manifested by sinus bradycardia, polymorphic ventricular tachycardia such as "pirouette", cardiac arrest, circulatory disorders and liver function, marked decrease in blood pressure.

Treatment - symptomatic (with bradycardia - the use of beta-adrenomimetics or the installation of a pacemaker, with a polymorphic ventricular tachycardia such as "pirouette" - intravenous injection of magnesium salts, pacing). Neither amiodarone, nor its metabolites are removed during hemodialysis. There is no specific antidote.

Interaction:

Pharmacodynamic interaction

Drugs that can cause polymorphic ventricular tachycardia of the typhus "pirouette"

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

These include:

- antiarrhythmic drugs: IA (quinidine, hydroquinidine, disopyramide, procainamide), sotalol, beprideil;

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

Drugs that can increase the duration of the interval QT Joint use 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 (opportunity increased risk of developing polymorphic ventricular tachycardia such as "pirouette"); When using such combinations, it is necessary to regularly 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 automatic or conduction disorders

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.

Medicines that can cause hypokalemia

Unrecommended combinations

- With laxatives that stimulate intestinal peristalsis, which can cause hypokalemia, increasing the risk of developing polymorphic ventricular tachycardia such as pirouette. Along with amiodarone, laxatives of other pharmaceutical groups should be used.

Combinations that require caution when applying

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

- With systemic corticosteroids (glucocorticosteroids, mineralocorticosteroids) and tetracosactide.

- With amphotericin B (intravenous administration).

It is necessary to prevent the development of hypoglycemia, and if it occurs, restore to normal potassium levels in the blood, monitor the electrolyte content in the blood and the ECG (for possible lengthening of the interval QT), and in the case of a polymorphic ventricular tachycardia like pirouette, antiarrhythmic drugs should not be used (ventricular pacing should be started, intravenous magnesium salts may be introduced).

Medicines for general anesthesia

The possibility of developing the following serious complications in patients taking amiodarone, with general anesthesia: bradycardia (resistant to atropine), arterial hypotension, conduction disorders, reduction in 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 or other drugs

Amiodarone and / or its metabolite desethylamiodarone inhibit isoenzymes CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-gp and can 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.

Medicines that are substrates P-gp

Amiodarone is an inhibitor P-gp. It is expected that its joint 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 digoxin and 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. Can a reduction in the dosage of digoxin is required.

- 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.

Medicines that are the 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 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 monitored prothrombin time [International Normalized Ratio (INR)] and corrected for 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.

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

When combined amiodarone, inhibitor of isoenzyme CYP3A4, with these drugs, an increase in their plasma concentrations is possible, which may 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 can increase the concentration of cyclosporine in the blood plasma, it is necessary to correct the dose of cyclosporine.

- Fentanyl

Combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of 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.

It is recommended the use of statins that are not metabolized by isoenzyme CYP3A4.

- Other drugs metabolized by isoenzyme CYP3A4: lidocaine (risk of developing sinus bradycardia and neurological 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 can theoretically increase the plasma concentration of dextromethorphan in the blood.

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

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 taking inhibitors of the isoenzyme CYP3A4 (for example, grapefruit juice and certain medicines such as cimetidine and HIV protease inhibitors (incl. 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 potent inducer of isoenzyme CYP3A4, when combined with amiodarone, it can reduce the plasma concentrations of amiodarone and desethylamiodarone.

- Preparations of St. John's Wort

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

Other drug interactions with amiodarone (see section "Special instructions")

- With sophosbuvir in monotherapy or in combination with other direct exposure antivirals against viral hepatitis C, such as daklataswir, simeprevir, ladypasvir

It is not recommended simultaneous use of amiodarone with sophosbuvir in monotherapy or in combination with other antiviral drugs of direct action against viral hepatitis C, such as daklataswir, simeprevir, lepidavir, as this can lead to the development of a severe bradycardia with clinical symptoms.

The mechanism of development of this bradycardia is unknown. If simultaneous use of these drugs can not be avoided, cardiac monitoring is recommended (see section "Special instructions").

Special instructions:

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

Intravenous jet administration of the drug Amiodarone should be performed only in the intensive care unit with constant monitoring of the ECG (due to the possibility of developing excessive bradycardia and arrhythmogenic action) and blood pressure (in connection with the possibility of lowering blood pressure).

In order to avoid the occurrence of reactions at the injection site (see the section "Side effect"), the drug Amiodarone it is recommended to enter through a central venous catheter. Only in the case of cardiac recovery in case of cardiac arrest,caused by ventricular fibrillation, resistant to defibrillation, in the absence of central venous access (no established central venous catheter), the drug Amiodarone can be injected into a large peripheral vein with maximum blood flow. If it is necessary to continue treatment with the drug Amiodarone after cardioversion, the drug Amiodarone should be injected intravenously via a central venous catheter under constant monitoring of blood pressure and ECG.

A drug Amiodarone Do not mix in one syringe or dropper with other medications. Do not inject other drugs into the same line of the infusion system as the drug Amiodarone (see section "Method of administration and dose").

Reactions from the heart

There were reports of new rhythm disturbances or weighting of already existing rhythm disturbances, sometimes with a fatal outcome. It is very important to make a differential diagnosis between the insufficient efficacy of the drug and its arrhythmogenic action, combined or not with aggravation of the severity of cardiovascular pathology. When using the drug Amiodarone about arrhythmogenic action was reported significantly less often than with the use of other antiarrhythmic drugs and, as a rule, it was observed in the presence of factors that increase the duration of the interval QT, such as interaction with other drugs and / or violations of the electrolytes in the blood (see the sections "Side effects" and "Interaction with other drugs"). Despite the ability of the drug Amiodarone increase the duration of the interval QT, he showed low activity with respect to the provocation of a polymorphic ventricular tachycardia of the "pirouette" type.

Pronounced bradycardia (see section "Interaction with other drugs").

When using Amiodarone in combination with sophosbuvir in combination with other antiviral drugs, direct action against viral hepatitis C, such as daklataswir, simeprevir, ladispavir, there have been cases of development of a pronounced, potentially life-threatening, bradycardia, as well as blockade of the heart. Therefore, the simultaneous use of these drugs with the drug Amiodarone Not recommended.If you can not avoid the simultaneous use of these drugs with the drug Amiodarone, careful monitoring of patients after the initiation of taking sophosbuvira in combination with other antiviral drugs of direct action is recommended. After the start of simultaneous application of sophosbuvir, patients who are at high risk for bradyarrhythmia should be continuously monitored in a hospital for at least 48 hours.

Due to the long half-life of amiodarone, appropriate monitoring should also be carried out in patients who stopped taking the drug Amiodarone in the last few months prior to commencement of treatment with sophosbuvir in combination with other antiviral drugs of direct action.

Patients taking the above drugs against viral hepatitis C in combination with the drug Amiodarone, both concomitantly with other drugs that slow heart rate, and without combining with such medications, should be informed of the symptoms indicating the development of bradycardia and heart block.If they occur, they should immediately seek medical help.

Pulmonary violations

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 the drug Amiodarone. If suspected development of interstitial pneumonitis in patients who experience severe dyspnea, 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. Reassess the need for the drug Amiodarone, since with the early cancellation 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, patients who were injected with Amiodarone, in very rare cases, usually immediately after surgery, there was a serious respiratory complication (acute adult respiratory distress syndrome), sometimes fatal; it is possible to link its development with interaction with high concentrations of oxygen (see section "Side effect").

Violation of the liver

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

Clinical and laboratory signs of chronic liver failure in the use of the drug Amiodarone Inside can be minimally expressed (hepatomegaly, increased activity of transaminases, 5 times higher than the upper limit of the norm) and reversible after drug withdrawal, but reports of deaths have been reported.

Severe bullous reactions

Treatment with drug Amiodarone should immediately stop when symptoms and manifestations appear that threaten life or even fatal reactions in the form of Stevens-Johnson syndrome, toxic epidermal necrolysis, namely: the appearance of progressive skin rash, often with the formation of blisters, or the appearance of mucosal lesions.

Disturbances on the part of the organ of sight

If there is a decrease in visual acuity or blurred vision, you should immediately perform a complete ophthalmological examination, including fundoscopy (examination of the fundus). The manifestation of neuropathy and / or neuritis of the optic nerve requires the abolition of amiodarone because of the possible development of blindness.

Drug Interactions

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

Hypokalemia

Hypokalemia should be adjusted before the drug is started Amiodarone.

Children

In children, the safety and efficacy of the drug Amiodarone not studied. In ampoules of the drug Amiodarone contains 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 arterial pressure, bradycardia and collapse.

General and local anesthesia

Before surgery, an anesthesiologist should be informed that the patient was given a drug Amiodarone. Treatment with drug Amiodarone can increase the hemodynamic risk inherent in local or general anesthesia (in particular, this refers to a decrease in heart rate, a decrease in conduction, and a decrease in heart contractility.)

Thyroid dysfunction

A drug Amiodarone can cause thyroid dysfunction, especially in patients with thyroid dysfunction in their own or family history. Therefore, in the case of a transition from the internal administration of the drug Amiodarone for taking the drug Amiodarone inside, both during treatment, and for several months after the end of treatment, careful clinical and laboratory testing 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).

A drug Amiodarone 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 determining the concentration of T3, T4 and TSH in blood plasma.

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

There is no evidence that amiodarone violates the ability to engage in activities that require increased concentration and speed of psychomotor reactions.However, as a precaution, patients with paroxysms of severe rhythm disturbances during drug treatment Amiodarone it is desirable to refrain from such activities.

Form release / dosage:

Concentrate for the preparation of a solution for intravenous administration of 50 mg / ml.

Packaging:

By 3 ml into ampoules of neutral glass or glass with resistance class hydrolysis HGA1 (first hydrolytic).

5 ampoules are placed in a contiguous cell pack of a polyvinylchloride (PVC) film or a polyethylene terephthalate (PET) film.

1 or 2 contour mesh packages together with the instruction for use and the ampoule scarifier are placed in a pack of cardboard for consumer containers.

5 or 10 ampoules together with the instruction for use and the ampoule scarifier are placed in a pack of cardboard for consumer packaging with a corrugated liner. When using ampoules with a dot or a ring of fracture, the ampoule scaper is not inserted.

Packing length of hospitals. 4, 5 or 10 contour mesh packages together with instructions for use in an amount equal to the number of contour mesh packages are placed in a pack of cardboard for consumer containers.

50 or 100 contour mesh packages together with an equal number of instructions for use are placed in a box of corrugated cardboard.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004223

Date of registration:30.03.2017

Expiration Date:30.03.2022

The owner of the registration certificate:ELLARA, LTD. ELLARA, LTD. Russia

Manufacturer: & nbsp

ELLARA, LTD. Russia

Information update date: & nbsp11.05.2017

Illustrated instructions

Instructions

Amiodarone (Amiodarone)