Amiodarone course of treatment. The drug Amiodarone - reviews

Country of origin

Product group

Antiarrhythmic drug

Release form

• 10 - blisters (6) made of PP / aluminum foil - cardboard packs.

Description of the dosage form

• tablets

Pharmacokinetics

Special conditions

Composition

• Amiodarone 200mg; Auxiliary substances: lactose monohydrate, corn starch, povidone K25, colloidal silicon dioxide, magnesium stearate,

Amiodarone indications for use

• Prevention of relapses
• Life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be initiated in a hospital with close cardiac monitoring).
• Supraventricular paroxysmal tachycardias:
• - documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with organic heart disease;
• - documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients without organic heart disease, when antiarrhythmic drugs of other classes are not effective, or there are contraindications to their use;
• - documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome;
• - atrial fibrillation (atrial fibrillation) and atrial flutter.
• Prevention of sudden arrhythmic death in patients of the group high risk
• - patients after a recent transfer

Amiodarone contraindications

• - weakness syndrome sinus node(sinus bradycardia and sinoatrial blockade, in the absence of an artificial pacemaker (risk of "stopping" the sinus node);
• - atrioventricular blockade II-III degree, two- and three-beam blockade (in the absence of an artificial pacemaker - a pacemaker);
• - hypokalemia, hypomagnesemia;
• - thyroid dysfunction (hypothyroidism, hyperthyroidism);
• - interstitial lung disease;
• - congenital or acquired prolongation of the QT interval;
• - simultaneous use with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardia, including polymorphic ventricular tachycardia of the "pirouette" type (torsade de pointe): class IA antiarrhythmic drugs (quinidine, disopyramide, procainamide), class III antiarrhythmic drugs (dofetilide, ibutilide, bretylium tosylate); sotalol; other (non-antiarrhythmic) agents such as bepridil; vincamine; some antipsychotics: phenothiazines (chlorpromazine, cyamemazine

Amiodarone side effects

• Development frequency side effects set out in accordance with the following gradation: very frequent - more than 10%, frequent - from 1 to 10%, infrequent - from 0.1% to 1%, rare - from 0.01 to 0.1%, very rare - less than 0.01%.
• From the side of the cardiovascular system
• frequent: moderate bradycardia (dose-dependent);
• infrequent: sinoatrial and AV blockade of various degrees, proarrhythmic effect (the occurrence of new or aggravation of existing arrhythmias, including cardiac arrest);
• very rare: severe bradycardia, sinus arrest (in patients with sinus node dysfunction and elderly patients), progression of chronic heart failure (with prolonged use), ventricular fibrillation / flutter.
• From the digestive system
• very common: nausea, vomiting, loss of appetite, dullness or loss of taste, dysgesia (metallic taste in the mouth), a feeling of heaviness in the epigastrium, an isolated increase in the activity of "liver" transaminases (1.5-3 times higher than normal), usually moderate and decreasing with dose reduction or even spontaneously;
• frequent: acute toxic hepatitis with an increase in the activity of "liver" transaminases and / or jaundice, including the development of liver failure, incl. fatal;
• very rare: chronic liver failure (pseudo-alcoholic hepatitis, cirrhosis), incl. fatal, pancreatitis.

drug interaction

Storage conditions

• keep away from children

Amiodarone- class III antiarrhythmic drug (repolarization inhibitor). It also has antianginal, coronary-dilating, alpha- and beta-adrenergic blocking, thyrotropic and hypotensive effects.
The antiarrhythmic effect is due to the effect on the electrophysiological processes of the myocardium; lengthens the action potential of cardiomyocytes; increases the effective refractory period of the atria, ventricles, atrioventricular (AV) node, bundle of His and Purkinje fibers, additional pathways for conducting excitation. By blocking "fast" sodium channels, it has effects characteristic of class I antiarrhythmics. It inhibits the slow (diastolic) depolarization of the sinus node cell membrane, causing bradycardia and a decrease in AV conduction.
The antianginal effect is due to coronary dilating and antiadrenergic action, a decrease in myocardial oxygen demand. It has an inhibitory effect on alpha- and beta-blockers of the cardiovascular system (without their complete blockade). Decreases sensitivity to sympathetic hyperstimulation nervous system, resistance of coronary vessels; increases coronary blood flow; slows down the heart rate; increases the energy reserves of the myocardium) by increasing the content of creatine sulfate, adenosine and glycogen).
It is similar in structure to thyroid hormones. The iodine content is about 37% of its molecular weight. It affects the metabolism of thyroid hormones, inhibits the conversion of T3 to T4 (thyroxine-5-deiodinase blockade) and blocks the uptake of these hormones by cardiocytes and hepatocytes, which leads to a weakening of the stimulating effect of thyroid hormones on the myocardium (E3 deficiency can lead to its hyperproduction and thyrotoxicosis). The onset of action (even when using "loading" doses) is from 2-3 days to 2-3 months, the duration of action varies from several weeks to months (determined in blood plasma for 9 months after discontinuation).

Pharmacokinetics

Indications for use

Mode of application

Outpatient - initial dose (divided into several doses) 600-800 mg / day - until a total dose of 10 g is reached (usually within 10-14 days).
maintenance dose. With maintenance treatment, the minimum effective dose is used, depending on the individual response of the patient, and usually ranges from 100 to 400 mg / day (1/2-2 tablets). Due to the long T1 / 2, the drug can be taken every other day or take a break in taking the drug - 2 days a week.
The average therapeutic single dose is 200 mg.
Average therapeutic daily dose- 400 mg.
The maximum single dose is 400 mg.
The maximum daily dose is 1200 mg.

Side effects

Contraindications

Pregnancy

Interaction with other drugs

Overdose

Storage conditions

Release form

Composition

Additionally

main parameters

tablets

C.01.B.D.01 Amiodarone

2 years.

Do not use after the expiry date stated on the packaging.

Amiodarone is undoubtedly the most effective of the existing antiarrhythmic drugs (AARPs). It is even called "arrhythmolytic drug". Although amiodarone was synthesized in 1960, and reports of its antiarrhythmic activity first appeared in 1969, to date, none of the new AARP can be compared with its effectiveness. Amiodarone accounts for about 25% of the total number of appointments of all AAPs.

Amiodarone has the properties of all four classes of AARP and, in addition, has a moderate α-blocking and antioxidant effect. However, the main antiarrhythmic property of amiodarone is the prolongation of the action potential and the effective refractory period of all parts of the heart.

However, the attitude of cardiologists to amiodarone from the very beginning of its use for the treatment of arrhythmias was very controversial. Due to the large list of extracardiac side effects, amiodarone, despite the fact that its high antiarrhythmic efficacy was already known, was considered a reserve drug for a long time: it was recommended to use it only for life-threatening arrhythmias and only in the absence of effect from all other antiarrhythmic drugs. The drug has gained a "reputation" of the "last resort", used "only for the treatment of life-threatening arrhythmias", "reserve drug" (L. N. Horowitz, J. Morganroth, 1978; J. W. Mason, 1987; J. C. Somberg, 1987).

After a series of studies, including CAST, it was found that while taking class I AAP, mortality in patients with organic lesion hearts can grow more than 3 times; it turned out that amiodarone is not only the most effective, but also the safest (after β-blockers) AARP. Numerous large controlled studies of the efficacy and safety of the use of amiodarone not only did not reveal an increase in overall mortality, on the contrary, a decrease in this indicator and the frequency of arrhythmic and sudden death was found. The incidence of arrhythmogenic effects, in particular ventricular tachycardia of the "pirouette" type, while taking amiodarone is less than 1%, which is much lower than when taking other anti-anxiety agents that prolong the QT interval. For comparison: the arrhythmogenic effect of sotalol hydrochloride in patients with ventricular arrhythmias is 4-5%, and the arrhythmogenic effect of foreign class Ic drugs reaches 20% or more. Thus, amiodarone has become the drug of first choice in the treatment of arrhythmias. Amiodarone is the only AARP whose administration, according to well-known cardiologists, is considered the safest for outpatient treatment, even in patients with organic heart disease. The arrhythmogenic effect of amiodarone is rarely observed, and this does not allow revealing a significant relationship between the occurrence of arrhythmogenic effects and the presence of organic heart damage (E. M. Prystovsky, 1994, 2003; L. A. Siddoway, 2003).

It should be emphasized that amiodarone is the only drug that is safe to use in heart failure. For any arrhythmias requiring treatment in patients with heart failure, the appointment of amiodarone is primarily indicated. Moreover, in acute heart failure or decompensation of chronic heart failure with a high heart rate (HR) (sinus tachycardia or tachysystole with atrial fibrillation), when the use of β-blockers is contraindicated, and the appointment of digoxin is ineffective and leads to dangerous consequences, slowing heart rate, improvement of hemodynamics and the patient's condition can be achieved with amiodarone.

side effects of amiodarone

As already noted, the main disadvantage of amiodarone is the likelihood of developing many extracardiac side effects, which are observed in 10-52% of patients with long-term use of the drug. However, the need to cancel amiodarone occurs in 5-25% of patients (J. A. Johus et al., 1984; J. F. Best et al., 1986; W. M. Smith et al., 1986). The main side effects of amiodarone include: photosensitivity, skin discoloration, thyroid dysfunction (both hypothyroidism and hyperthyroidism), increased transaminase activity, peripheral neuropathy, muscle weakness, tremor, ataxia, visual disturbances. Almost all of these side effects are reversible and disappear after discontinuation or with a decrease in the dose of amiodarone.

Thyroid function disorders are observed in 10% of cases. However, it is much more common to see subclinical hypothyroidism. Hypothyroidism can be controlled with levothyroxine. Hyperthyroidism requires withdrawal of amiodarone (with the exception of life-threatening arrhythmias) and treatment of hyperthyroidism (I. Klein, F. Ojamaa, 2001).

The most dangerous side effect of amiodarone is lung damage - the occurrence of interstitial pneumonitis or, less commonly, pulmonary fibrosis. According to various authors, the incidence of lung damage ranges from 1 to 17% (J. J. Heger et al., 1981; B. Clarke et al., 1985, 1986). However, these data were obtained in the 1970s, when amiodarone was prescribed for a long time and in high doses. In most patients, lung damage develops only with long-term use of relatively large maintenance doses of amiodarone - more than 400 mg / day (up to 600 or even 1200 mg / day). In Russia, such doses are used extremely rarely, usually the maintenance daily dose is 200 mg (5 days a week) or even less. Currently, the incidence of "amiodarone lung injury" is no more than 1% per year. In one study, the incidence of lung injury while taking amiodarone and taking placebo did not differ (S. J. Connolly, 1999; M. D. Siddoway, 2003). Clinical manifestations of "amiodarone lung disease" resemble an acute infectious lung disease: the most common complaint is shortness of breath, while there is a slight increase in temperature, cough, and weakness. Radiologically, diffuse interstitial infiltration of the lung tissue is noted, localized changes can be observed, including the so-called “air-containing blackouts” (J. J. Kennedy et al., 1987). Treatment of "amiodarone lung disease" consists in the abolition of amiodarone and the appointment of corticosteroids.

The main regimens of amiodarone therapy

It is necessary to dwell separately on some features of the use of amiodarone. For the onset of the antiarrhythmic effect of amiodarone, a period of "saturation" is necessary.

Amiodarone intake. In Russia, the most common regimen for the appointment of amiodarone is 600 mg/day (3 tablets per day) for 1 week, then 400 mg/day (2 tablets per day) for another 1 week, maintenance dose - long-term 200 mg per day (1 tablet per day) or less. A faster effect can be achieved by prescribing the drug at a dose of 1200 mg / day for 1 week (6 tablets per day), then a gradual dose reduction to 200 mg per day or less. One of the schemes recommended in the international guidelines on cardiology Heart Disease (2001): taking amiodarone for 1-3 weeks at 800-1600 mg / day (i.e. 4-8 tablets per day), then taking 800 mg (4 tablets) for 2-4 weeks, after that - 600 mg / day (3 tablets) for 1-3 months and then switching to maintenance doses - 300 mg / day or less (titration depending on sensitivity patient to the lowest effective dose).

There are reports of the effective use of high loading doses of amiodarone - 800-2000 mg 3 times a day (i.e. up to 6000 mg / day - up to 30 tablets per day) in patients with severe, refractory to other methods of treatment, life-threatening ventricular arrhythmias with repeated episodes of ventricular fibrillation (ND Mostow et al., 1984; SJL Evans et al., 1992). A single dose of amiodarone at a dose of 30 mg/kg of body weight is officially recommended as one of the methods of recovery. sinus rhythm with atrial fibrillation.

Thus, the use of large loading doses of amiodarone is relatively safe and effective. To achieve an antiarrhythmic effect, it is not necessary to achieve a stable concentration of the drug in the body. Short-term administration of high doses may even be safer than long-term use the drug in smaller daily doses, and allows you to quickly assess the antiarrhythmic efficacy of the drug (L. E. Rosenfeld, 1987). It can be recommended during the period of "saturation" taking amiodarone at a dose of 1200 mg / day during the first week. After reaching the antiarrhythmic effect, the dose is gradually reduced to the minimum effective. It has been shown that effective maintenance doses of amiodarone can be 100 mg/day and even 50 mg/day (A. Gosselink, 1992; M. Dayer, S. Hardman, 2002).

Intravenous administration of amiodarone. Efficiency intravenous use amiodarone is less studied. When administered intravenously as a bolus, amiodarone is usually administered at a rate of 5 mg/kg body weight over 5 minutes. In recent years, slower intravenous administration of amiodarone has been recommended. With rapid administration, a decrease in the effectiveness of the drug may occur due to vasodilation, lowering blood pressure and activation of the sympathetic nervous system. One of the most popular schemes intravenous administration amiodarone: bolus 150 mg over 10 minutes, then infusion at a rate of 1 mg / min for 6 hours (360 mg over 6 hours), then - infusion at a rate of 0.5 mg / min. However, there is evidence of safe and effective intravenous administration of amiodarone at a dose of 5 mg/kg of body weight for 1 min or even 30 s (R. Hofmann, G. Wimmer, F. Leisch, 2000; D. E. Hilleman et al., 2002). The antiarrhythmic effect of amiodarone begins to appear within 20-30 minutes. Side effects with intravenous administration are rare and usually do not have symptoms. In 5% of patients, bradycardia is noted, in 16% - a decrease in blood pressure (L. E. Siddoway, 2003).

Interestingly, intravenous administration of amiodarone in terms of its effect on electrophysiological parameters differs sharply from taking a loading dose of the drug orally. When conducting an electrophysiological study after intravenous administration, only a slowdown in conduction along the AV node (an increase in the AN interval) and an increase in the refractory period of the AV node are noted. Thus, with intravenous administration of amiodarone, only an antiadrenergic effect occurs (there is no class III effect), while after taking a loading dose of amiodarone orally, in addition to slowing conduction through the AV node, there is an increase in the duration of the QT interval and effective refractory periods in all parts of the heart. (atria, AV node, His-Purkinje system, ventricles and accessory pathways). Based on these data, the effectiveness of intravenous administration of amiodarone in atrial and ventricular arrhythmias is difficult to explain (H. J. J. Wellens et al., 1984; R. N. Fogoros, 1997).

Intravenous amiodarone is administered into the central veins through a catheter, since prolonged administration into peripheral veins may cause phlebitis. With the introduction of the drug into the peripheral veins, immediately after the injection, quickly inject 20 ml of saline.

Principles of selection of effective antiarrhythmic therapy

In the absence of contraindications, amiodarone is the drug of choice for almost all arrhythmias requiring antiarrhythmic therapy. The use of amiodarone is advisable for all types of supraventricular and ventricular arrhythmias. The effectiveness of AARP in the treatment of the main clinical forms of arrhythmias is approximately the same: in the treatment of extrasystole in most of them, it is 50-75%, in therapy to prevent the recurrence of supraventricular tachyarrhythmias - from 25 to 60%, with severe ventricular tachycardia - from 10 to 40 %. In this case, one drug is more effective in some patients, and the other - in others. An exception is amiodarone - its effectiveness often reaches 70-80% even in arrhythmias refractory to other anti-anxiety drugs in this group of patients.

In patients with arrhythmias, but without signs of organic heart disease, the appointment of any AA is considered acceptable. In patients with organic disease heart disease (postinfarction cardiosclerosis, ventricular hypertrophy and/or dilatation of the heart), the first choice drugs are amiodarone and β-blockers. Numerous studies have established that the use of class I AAs in patients with organic heart disease is accompanied by a significant increase in mortality. Thus, amiodarone and β-blockers are not just the drugs of choice in patients with organic heart disease, but practically the only means for the treatment of arrhythmias.

Given the safety of AARP, it is advisable to start evaluating their effectiveness with β-blockers or amiodarone. If monotherapy is ineffective, the effectiveness of the combination of amiodarone and β-blockers is evaluated. If there is no bradycardia or prolongation of the PR interval, any β-blocker can be combined with amiodarone.

In patients with bradycardia, pindolol (Whisken) is added to amiodarone. It has been shown that the combined use of amiodarone and β-blockers reduces mortality in patients with cardiovascular diseases to a much greater extent than either drug alone. Some experts even recommend dual chamber stimulator implantation (in DDD mode) for safe amiodarone therapy in combination with β-blockers. Only in the absence of the effect of β-blockers and / or amiodarone, class I AAs are used. In this case, class I drugs, as a rule, are prescribed against the background of taking a β-blocker or amiodarone. The CAST study showed that co-administration of β-blockers eliminates the negative effect of class I AARP on the survival of patients with arrhythmias. In addition to class I drugs, it is possible to prescribe sotalol hydrochloride (β-blocker with the properties of a class III drug).

Combinations of amiodarone and other AAPs

In the absence of the effect of monotherapy, combinations of amiodarone are prescribed not only with β-blockers, but also with other AAPs. Theoretically, of course, the most rational is the combination of drugs with different mechanisms of antiarrhythmic action. For example, it is advisable to combine amiodarone with class Ic drugs: propafenone, lappaconitine hydrobromide, etacizine. Class I drugs do not prolong the QT interval. The simultaneous administration of drugs that have the same effect on the electrophysiological properties of the myocardium seems dangerous. For example, amiodarone and sotalol hydrochloride prolong the QT interval, so it is believed that when these drugs are taken simultaneously, the risk of an increase in the QT interval and the occurrence of associated ventricular tachycardia of the "pirouette" type increases. However, in combination therapy with AARP, they are prescribed in reduced doses. Therefore, we can expect both the absence of an effect of combination therapy on the frequency of arrhythmogenic effects, and a decrease in the frequency unwanted effects. In this regard, the results of one study are of interest, during which ibutilide (a drug that lengthens the QT interval, against the background of which the incidence of torsades de pointes reaches 8%) was administered to patients with recurrent atrial fibrillation who were constantly taking amiodarone. Restoration of sinus rhythm was achieved in 54% with atrial flutter and in 39% with atrial fibrillation. At the same time, only one case of pirouette-type tachycardia (1.4%) was noted in 70 patients. It should be noted that in this study, the administration of ibutilide was not stopped when the QT interval was prolonged or bradycardia occurred (K. Glatter et al., 2001). Thus, amiodarone may even reduce the risk of torsades de pointes when combined with class III agents. In this case, an explanation is obtained of reports of cases of relief of pirouette-type tachycardia with amiodarone, including in patients with congenital variants of QT interval prolongation. In addition, prolongation of the QT interval by 15% or more is one of the predictors of the effectiveness of amiodarone with its long-term administration.

An approximate sequence of AAT selection for recurrent arrhythmias in patients with organic heart disease can be represented as follows:

• β-blocker or amiodarone;
• β-blocker + amiodarone;
• sotalol hydrochloride;
• amiodarone + AARP Ic (Ib) class;
• β-blocker + any class I drug;
• amiodarone + β-blocker + AARP Ic (Ib) class;
• sotalol hydrochloride + AARP Ic (Ib) class.

The use of amiodarone in certain clinical forms of arrhythmias

Because amiodarone is the most effective drug in almost all types of cardiac arrhythmias, and especially if it is necessary to prevent recurrence of arrhythmias, the selection scheme for anti-recurrent AAT is applicable for all recurrent arrhythmias, from extrasystole to life-threatening ventricular tachyarrhythmias, up to "electrical storm".

Atrial fibrillation. Currently, due to high efficiency, good tolerability and ease of administration, the restoration of sinus rhythm in atrial fibrillation with a single oral dose of amiodarone is becoming increasingly important. The recommended dose for a single dose of the drug is 30 mg/kg of body weight. The average time to return to sinus rhythm after taking this dose is about 6 hours.

GE Kochiadakis et al (1999) compared two schemes for the use of amiodarone to restore sinus rhythm in atrial fibrillation: 1) on the first day - ingestion of 2 g of amiodarone (500 mg 4 times a day), on the second day - 800 mg (200 mg mg 4 times a day); 2) intravenous drip administration of amiodarone: 300 mg for 1 hour, then - 20 mg / kg during the first day, the second day - 50 mg / kg.

Restoration of sinus rhythm was observed in 89% of patients receiving oral amiodarone (scheme 1), in 88% with intravenous infusion of amiodarone (scheme 2), and in 60% of patients receiving placebo. With intravenous administration, there have been several cases of lowering blood pressure and the occurrence of thrombophlebitis. Oral amiodarone did not cause any side effects.

At the Department of Therapy of the Russian State Medical University, the effectiveness of a single oral dose of amiodarone (cordarone) at a dose of 30 mg/kg of body weight was studied in atrial fibrillation. Restoration of sinus rhythm was achieved in 80% of patients. At the same time, no significant side effects were noted (Janashiya et al., 1995, 1998; Khamitsaeva et al., 2002).

Amiodarone is the most effective drug for preventing recurrence of atrial fibrillation. In a direct comparison with sotalol hydrochloride and propafenone, amiodarone proved to be 1.5-2 times more effective than sotalol hydrochloride and propafenone (CTAF and AFFIRM studies).

There are reports of a very high efficacy of amiodarone even when administered to patients with severe heart failure (NYHA class III, IV): out of 14 patients, sinus rhythm persisted for 3 years in 13 patients (93%), and out of 25 patients - in 21 (84%) within 1 year (AT Gosselink et al., 1992; HR Middlekauff et al., 1993).

Ventricular tachycardia. For the relief of ventricular tachycardia, it is recommended to use: amiodarone - 300-450 mg intravenously, lidocaine - 100 mg intravenously, sotalol hydrochloride - 100 mg intravenously, procainamide - 1 g intravenously. After restoration of sinus rhythm, if necessary, infusion of effective AARP is carried out.

The intervals between the administration of each drug depend on the clinical situation. With severe hemodynamic disturbances, electrical cardioversion is performed at any stage. True, the authors of the international recommendations on cardiopulmonary resuscitation and emergency cardiology (2000) do not recommend the introduction of more than one drug, and in the absence of the effect of the first drug, they consider it appropriate to immediately apply electrical cardioversion.

The clinical efficacy of amiodarone in preventing the recurrence of ventricular tachyarrhythmias ranges from 39 to 78% (average 51%) (H. L. Greene et al., 1989; Golitsyn et al., 2001).

To characterize a particularly severe course of ventricular tachyarrhythmias, some "slang" terms are sometimes used, for example, "electrical storm" - recurrent unstable polymorphic ventricular tachycardia and / or ventricular fibrillation. Quantitative definitions, according to different authors, include from "more than 2 times within 24 hours" to "19 episodes within 24 hours or more than 3 episodes within 1 hour" (K. Nademanee et al., 2000). Patients with "electrical storm" undergo repeated defibrillation. One of the most effective ways to overcome this severe complication is the appointment of β-blockers in combination with intravenous administration and ingestion of large doses of amiodarone (up to 2 g or more per day). There are reports of the successful use of very large doses of amiodarone. In severe refractory to drug therapy (failure of lidocaine, bretylium tosylate, procainamide and other AADs) life-threatening recurrent ventricular tachyarrhythmias ("electrical storm"), amiodarone was successfully administered orally up to 4-6 g per day (50 mg/kg) for 3 days (i.e. 20-30 tablets), then 2-3 g per day (30 mg / kg) for 2 days (10-15 tablets) followed by a dose reduction (SJL Evans et al., 1992 ). If in patients with "electrical storm" the effect of intravenous administration of amiodarone is noted, which persists when switching to oral amiodarone, the survival rate of such patients is 80% during the first year (R. J. Fogel, 2000). When comparing the effectiveness of amiodarone and lidocaine in patients with refractory to electrical cardioversion and defibrillation of ventricular tachycardia, amiodarone was significantly more effective in terms of increasing the survival of such patients (P. Dorian et al., 2002).

The second term used to refer to the severe course of tachycardia is the term incessant ("continuous", "persistent", "intractable", "incessant") - continuously recurrent monomorphic ventricular tachycardia of severe course. In this variant of the course of ventricular tachycardia, combinations of antiarrhythmic drugs are used, for example, amiodarone in combination with lidocaine, mexiletine, or class Ia and Ic antiarrhythmics. There are reports of the effectiveness of the blockade of the left stellate ganglion. There are also data on the high efficiency of intra-aortic balloon counterpulsation. With this procedure, a complete cessation of recurrent tachycardia is achieved in 50% of patients, and a marked improvement in tachycardia control is achieved in 86% (E. C. Hanson et al., 1980; H. Bolooki, 1998; J. J. Germano et al., 2002).

Increased risk of sudden death. For a long period of time, the main method of therapy for patients with an increased risk of sudden death was the use of AARP. Most effective way selection of antiarrhythmic therapy, it was considered to evaluate its effectiveness using an intracardiac electrophysiological study and / or repeated daily ECG monitoring before and after the appointment of AARP.

In the CASCADE study in patients with sudden death, empiric amiodarone was also found to be much more effective than the use of class I drugs (quinidine, procainamide, flecainide) selected using repeated electrophysiological studies and ECG monitoring (respectively 41 and 20%) .

It has been established that to prevent sudden death, it is most advisable to prescribe β-blockers and amiodarone.

In the CAMIAT study, the use of amiodarone in postinfarction patients was accompanied by a significant reduction in arrhythmic mortality by 48.5% and cardiovascular mortality by 27.4%. The EMIAT study showed a significant reduction in arrhythmic mortality by 35%. A meta-analysis of 13 studies of the efficacy of amiodarone in postinfarction patients and patients with heart failure (ATMA) revealed a significant reduction in arrhythmic mortality by 29% and overall mortality by 13%.

Even more effective is the simultaneous administration of a β-blocker and amiodarone. Against the background of taking a β-blocker and amiodarone in patients with a myocardial infarction, there was an additional decrease in arrhythmic mortality by 2.2 times, cardiac mortality by 1.8 times and overall mortality by 1.4 times (EMIAT and CAMIAT studies). In some groups of patients, the effectiveness of amiodarone in reducing overall mortality is not inferior to implantable cardioverter defibrillators (ICD).

The ICD discharges are very painful (the pain experienced by the patient during the ICD discharge is commonly compared to "a horse's hoof kick in the chest"). The appointment of amiodarone to patients with ICD significantly reduces the frequency of defibrillator discharges - by reducing the frequency of arrhythmias. A recent OPTIC study compared the efficacy of using a β-blocker, a combination of amiodarone and a β-blocker, and sotalol hydrochloride to reduce the frequency of ICD shocks. The administration of a combination of amiodarone and β-blockers was 3 times more effective than the use of β-blockers in the form of monotherapy, and more than 2 times compared with taking sotalol hydrochloride (S. J. Connolly et al., 2006).

Thus, despite a number of shortcomings of the drug, amiodarone is still a first-choice AARP.

It should be noted that the use of generic forms of amiodarone is fraught with a lack of effectiveness of treatment and the development of complications (J. A. Reiffel and P. R. Kowey, 2000). A study by S. G. Kanorsky and A. G. Staritsky revealed a 12-fold increase in the frequency of atrial fibrillation recurrences when replacing the original drug with generics.

In the US and Canada, approximately 20,000 hospitalizations could be avoided each year as they result from replacing amiodarone with generic copies (P. T. Pollak, 2001).

P. H. Janashia,
N. M. Shevchenko, doctor of medical sciences, professor
T. V. Ryzhova
RSMU, Moscow

Composition (per 1 ml):

• Active ingredient: Amiodarone hydrochloride in terms of 100% substance - 50.0 mg;
• Excipients: Polysorbate 80 (Tween 80) - 100.0 mg; Benzyl alcohol - 20.0 mg; Water for injection - up to 1.0 ml.

Concentrate for solution for intravenous administration 50 mg/ml.

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

5 ampoules are placed in a blister pack made of polyvinyl chloride (PVC) film or polyethylene terephthalate (PET) film.

1 or 2 blister packs, together with instructions for use and an ampoule scarifier, are placed in a pack of cardboard for consumer packaging.

5 or 10 ampoules, together with instructions for use and an ampoule scarifier, are placed in a pack of cardboard for consumer packaging with a corrugated liner.

When using ampoules with a break point or ring, the ampoule scarifier is not inserted.

Packaging for hospitals. 4, 5 or 10 blisters, together with instructions for use in an amount equal to the number of blisters, are placed in a pack of cardboard for consumer packaging.

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

Description of the dosage form

Clear, yellowish solution.

pharmachologic effect

Antiarrhythmic agent.

Pharmacokinetics

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

Communication 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, deethylamiodarone, is pharmacologically active and may enhance the antiarrhythmic effect of the parent compound.

Amiodarone and desethylamiodarone in vitro have the ability to inhibit CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8 isoenzymes. Amiodarone and deethylamiodarone are also able to inhibit certain transporters (P-glycoprotein-P-gp) and the organic cation transporter (OC2). In vivo, the interaction of amiodarone with substrates of CYP3A4, CYP2C9, CYP2D6 and P-gp isoenzymes was observed.

It is excreted very slowly, mainly with bile through the intestines. Amiodarone and its metabolites are determined in the blood plasma for 9 months after stopping treatment. Amiodarone and its metabolites are not subject to dialysis.

Pharmacodynamics

Amiodarone belongs to class III antiarrhythmic drugs (a class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action, tk. 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 a non-competitive beta-adrenergic blocking effect.

In addition to the antiarrhythmic action, it has antianginal, coronary dilating, alpha and beta adrenoblocking effects.

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

Antiarrhythmic properties are due to:

• An increase in the duration of the 3rd phase of the action potential of cardiomyocytes (mainly due to blocking the ion current in potassium channels - the effect of an antiarrhythmic agent of class III according to Williams classification);
• Decreased automatism of the sinus node, leading to a decrease in heart rate (HR);
• Non-competitive blockade of alpha and beta adrenergic receptors;
• Deceleration of intracardiac (sinoatrial, atrial and atrioventricular - AV) conduction. This action is more pronounced with tachycardia. Amiodarone does not have a significant effect on intraventricular conduction;
• An increase in the duration of the refractory period and a decrease in the excitability of atrial and ventricular myocardiocytes, as well as an increase in the duration of the refractory period of the AV node;
• Slowing the speed of conduction and an increase in the duration of the refractory period in additional bundles of atrioventricular conduction.

Other effects of amiodarone:

• Reducing myocardial oxygen consumption due to a moderate decrease in total peripheral vascular resistance (OPVR) and heart rate, as well as myocardial contractility;
• An increase in coronary blood flow due to a direct effect on the tone of the coronary arteries;
• Maintaining the value of cardiac output, despite a slight decrease in myocardial contractility (due to a decrease in peripheral vascular resistance and afterload);
• Influence on the metabolism of thyroid hormones: inhibition of the conversion of T3 to T4 (blockade of thyroxine-5-deiodinase) and blocking the capture of these hormones by myocardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones;
• Recovery of cardiac activity in cardiac arrest caused by defibrillation-resistant ventricular fibrillation.

Indications for use Amiodarone

Relief of attacks of paroxysmal tachyarrhythmia:

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

Relief of attacks of paroxysmal and permanent form of atrial fibrillation (atrial fibrillation) and atrial flutter.

Cardiac resuscitation in cardiac arrest caused by defibrillation-resistant ventricular fibrillation.

Contraindications for the use of amiodarone

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

• Intravenous jet administration is contraindicated in case of arterial hypotension, severe respiratory failure (these conditions may be aggravated).
• Hypersensitivity to iodine, amiodarone or excipients of the drug.
• Weak sinus syndrome (sinus bradycardia, sinoatrial block), except when using an artificial pacemaker (danger of "stopping" the sinus node).
• AV block II-III degree in the absence of a permanent artificial pacemaker.
• Violations of intraventricular conduction (two- and three-beam blockade) in the absence of a permanent artificial pacemaker (pacemaker). With such conduction disorders, the use of the drug Amiodarone intravenously is possible only in specialized departments under the cover of a temporary pacemaker (pacemaker).
• Simultaneous use with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardia, including polymorphic ventricular tachycardia of the "pirouette" type:
• antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide, procainamide); class III antiarrhythmic drugs (dofetilide, ibutilide, bretylium tosylate); sotalol; bepridil;
• other (non-antiarrhythmic) drugs such as vincamine, some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, veraliprid), butyrophenones (droperidol, haloperidol), sertindole , pimozide; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular, erythromycin when administered intravenously, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine when administered parenterally; diphemanil methyl sulfate; mizolastin; astemizole, terfenadine; fluoroquinolones.
• Congenital or acquired prolongation of the QT interval.
• Pronounced decrease in blood pressure (BP), cardiogenic shock, collapse.
• Hypokalemia, hypomagnesemia.
• Thyroid dysfunction (hypothyroidism, hyperthyroidism).
• Pregnancy, breastfeeding period.
• Age up to 18 years (efficacy and safety not established).

Carefully

Arterial hypotension, cardiomyopathy, severe decompensated heart failure (III-IV functional class according to the classification of the New York Heart Association (NYHA)), severe respiratory failure against the background of interstitial lung diseases, liver failure, bronchial asthma, old age (high risk of developing severe bradycardia ), AV block I degree.

Amiodarone Use in pregnancy and children

Pregnancy

Currently available clinical information is insufficient to determine the possibility or impossibility of malformations 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, it is not expected to be affected by amiodarone if it is used earlier. Excess iodine when using the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in newborns or even to the formation of a clinically significant goiter in him.

Due to the potential impact on thyroid gland fetal amiodarone is contraindicated during pregnancy, unless the expected benefit of its use by a pregnant woman outweighs the risks to the fetus (for life-threatening ventricular arrhythmias).

breastfeeding period

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

Amiodarone side effects

The frequency of side effects was determined in accordance with the classification of the World Health Organization (WHO): very often (> 10%), often (> 1%, 0.1%, 0.01%,

Blood disorders and lymphatic system: Frequency unknown - Neutropenia, agranulocytosis.

Cardiovascular disorders: Often - Bradycardia, usually moderate; Decreased blood pressure is usually mild and transient. With an overdose or too rapid administration of the drug, cases of a pronounced decrease in blood pressure or collapse were observed. Very rarely - Arrhythmogenic effect (the emergence of new arrhythmias, or aggravation of existing arrhythmias, in some cases with subsequent cardiac arrest); Severe bradycardia, sinus arrest 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. The frequency is unknown - Polymorphic ventricular tachycardia of the "pirouette" type.

Endocrine system disorders: Very rare - Syndrome of inappropriate secretion of antidiuretic hormone (SIAH); Frequency unknown - Hyperthyroidism.

Gastrointestinal disorders: Very rare - Nausea. Frequency unknown - Pancreatitis/acute pancreatitis.

General disorders and disorders at the injection site: Often - Reactions at the injection site, such as pain, erythema, edema, necrosis, extravasation, infiltration, inflammation, induration, thrombophlebitis, phlebitis, cellulitis, infection, changes in skin pigmentation.

Liver and biliary tract disorders: Very rare - An isolated increase in the activity of "liver" transaminases in the blood serum, usually moderate (exceeding upper bound norms from 1.5 to 3 times), observed at the beginning of treatment. The activity of "liver" transaminases may return to normal values ​​with a decrease in dose or even spontaneously; Acute liver damage with increased activity of "liver" transaminases and / or jaundice, including the development of liver failure, sometimes fatal.

Violations by immune system: Very rare - Anaphylactic shock. Frequency unknown - Angioedema (Quincke's edema).

Disorders of the musculoskeletal and connective tissue: Frequency unknown - Pain in the lumbar and lumbosacral spine.

Nervous system disorders: Very rare - Benign intracranial hypertension (pseudotumor of the brain), headache.

Psychiatric disorders: Frequency unknown - State of confusion / delirium, hallucinations.

Violation of the genital organs and mammary gland: Frequency unknown - Decreased libido.

Respiratory, thoracic and mediastinal disorders: Very rare - Interstitial pneumonitis or fibrosis, sometimes fatal; Severe respiratory complications (acute adult respiratory distress syndrome), sometimes fatal; Bronchospasm and / or apnea in patients with severe respiratory failure, especially in patients with bronchial asthma.

Skin and subcutaneous tissue disorders: Very rare - 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.

On the part of the organ of vision: the frequency is unknown - optic neuropathy / neuritis, which can progress to blindness.

drug interaction

Pharmacodynamic interaction

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

Combination therapy with drugs that can cause torsades de pointes is contraindicated, as it increases the risk of potentially fatal torsades de pointes.

These include:

• antiarrhythmic drugs: IA (quinidine, hydroquinidine, disopyramide, procainamide), sotalol, bepridil;
• other (non-antiarrhythmic) drugs such as: vincamine; some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levopromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, veraliprid), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin when administered intravenously, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine when administered parenterally; diphemanil methyl sulfate; mizolastin; astemizole; terfenadine.

Medicines that can prolong the QT interval

Co-administration of amiodarone with drugs that can increase the duration of the QT interval should be based on a careful assessment for each patient of the ratio of expected benefit and potential risk (possibility of increasing the risk of developing polymorphic ventricular tachycardia of the "pirouette" type); when using such combinations, it is necessary to regularly monitor the ECG of patients (to detect prolongation of the QT interval), as well as the content of potassium and magnesium in the blood.

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

Medicines that reduce heartbeat or causing disturbances in automatism or conduction

Combination therapy with these drugs is not recommended. Beta-blockers, blockers of "slow" calcium channels that slow down the heart rate (verapamil, diltiazem), can cause disturbances in automatism (development of excessive bradycardia) and conduction.

Drugs that can cause hypokalemia

With laxatives that stimulate intestinal motility, which can cause hypokalemia, increasing the risk of developing polymorphic ventricular tachycardia of the "pirouette" type. Simultaneously with amiodarone, laxatives of other pharmaceutical groups should be used.

Combinations requiring caution when using

With diuretics that cause 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 in case of its occurrence, to restore the potassium content in the blood to normal values, to control the content of electrolytes in the blood and ECG (for possible prolongation of the QT interval), and in case of polymorphic ventricular tachycardia of the "pirouette" type, one should not use antiarrhythmic drugs (ventricular pacing should be started; intravenous administration of magnesium salts is possible).

Medicines for general anesthesia

The following severe complications have been reported in patients taking amiodarone during general anesthesia: bradycardia (resistant to atropine), arterial hypotension, conduction disturbances, decreased cardiac output.

There have been very rare cases of severe respiratory complications, sometimes fatal (adult acute respiratory distress syndrome), which developed immediately after surgery, the occurrence of which is associated with interaction with high oxygen concentrations.

Heart rate slowing drugs (clonidine, guanfacine; cholinesterase inhibitors [donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide], pilocarpine)

Risk of developing excessive bradycardia (cumulative effects).

Effect of amiodarone on other medicinal products

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

Drugs that are P-gp substrates

Amiodarone is a P-gp inhibitor. It is expected that its co-administration with drugs that are P-gp substrates 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 atrioventricular conduction. In addition, the combination of digoxin with amiodarone may increase the concentration of digoxin in the blood plasma (due to a decrease in its clearance). Therefore, when combining digoxin with amiodarone, it is necessary to determine the concentration of digoxin in the blood and monitor possible clinical and electrocardiographic manifestations of digitalis intoxication. Doses of digoxin may need to be reduced.

Dabigatran

Caution should be exercised when co-administering amiodarone with dabigatran due to the risk of bleeding. The dose of dabigatran may need to be adjusted as directed in its prescribing information.

Drugs that are substrates of the CYP2C9 isoenzyme

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

warfarin

When warfarin is combined with amiodarone, it is possible to enhance the effects of an indirect anticoagulant, which increases the risk of bleeding. The prothrombin time [International Normalized Ratio (INR)] should be monitored more frequently and the doses of indirect anticoagulants should be adjusted both during and after amiodarone treatment.

Phenytoin

When phenytoin is combined with amiodarone, an overdose of phenytoin may develop, which can lead to neurological symptoms; clinical monitoring is necessary 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 CYP2D6 isoenzyme

Flecainide

Amiodarone increases the plasma concentration of flecainide by inhibiting the CYP2D6 isoenzyme, and therefore requires dose adjustment of flecainide.

Drugs that are substrates of the CYP3A4 isoenzyme

When combined with amiodarone, an inhibitor of the isoenzyme CYP3A4, with these drugs, an increase in their plasma concentrations is possible, which may lead to an increase in their toxicity and / or an increase in pharmacodynamic effects and may require a reduction in their doses. These drugs are listed below.

Cyclosporine

The combination of cyclosporine with amiodarone may increase the concentration of cyclosporine in blood plasma, 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.

HMG-CoA reductase inhibitors (statins) (simvastatin, atorvastatin and lovastatin)

Increased risk of muscle toxicity (rhabdomyolysis) with simultaneous use of amiodarone and statins metabolized by the CYP3A4 isoenzyme.

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

Drugs that are a substrate of CYP2D6 and CYP3A4 isoenzymes

Dextromethorphan

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

Clopidogrel

Clopidogrel is an inactive thienopyrimidine drug metabolized in the liver to active metabolites. An interaction between clopidogrel and amiodarone is possible, which may lead to a decrease in the effectiveness of clopidogrel.

Effect of other medicinal products on amiodarone

Inhibitors of CYP3A4 and CYP2C8 isoenzymes 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 CYP3A4 isoenzyme (for example, grapefruit juice and certain drugs, such as cimetidine and HIV protease inhibitors (including indinavir) during treatment with amiodarone. HIV protease inhibitors, while used with amiodarone, may increase the concentration of amiodarone in blood.

CYP3A4 isoenzyme inducers

Rifampicin

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

Hypericum perforatum preparations

St. John's wort is a powerful inducer of the CYP3A4 isoenzyme. In this regard, it is theoretically possible to reduce the plasma concentration of amiodarone and reduce its effect (clinical data are not available).

Other drug interactions with amiodarone

With sofosbuvir alone or in combination with others antiviral drugs direct action against viral hepatitis C, such as daclatasvir, simeprevir, ledipasvir

The simultaneous use of amiodarone with sofosbuvir in monotherapy or in combination with other direct-acting antiviral drugs against viral hepatitis C, such as daclatasvir, simeprevir, ledipasvir, is not recommended, as this can lead to the development of severe symptomatic bradycardia.

The mechanism by which this bradycardia develops is unknown. If concomitant use of these drugs cannot be avoided, cardiac monitoring is recommended.

Dosage of Amiodarone

Amiodarone (concentrate for solution for intravenous administration) is intended for use in cases where a rapid antiarrhythmic effect is required or its oral administration is not possible.

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

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

Due to the peculiarities dosage form the drug, you can not enter an infusion solution with a concentration of less than 0.6 mg / ml (2 ampoules in 500 ml of a 5% dextrose (glucose) solution).

To avoid local reactions, Amiodarone should be administered through a central venous catheter, except in cases of cardioresuscitation in defibrillation-resistant ventricular fibrillation, when the drug can be injected into large peripheral veins - in the absence of a central venous access.

Severe cardiac arrhythmias, in cases where it is impossible to take the drug by mouth (with the exception of cases of cardiac resuscitation during cardiac arrest caused by defibrillation-resistant ventricular fibrillation)

Intravenous drip through a central venous catheter

The usual loading dose is 5 mg/kg of body weight administered, if possible, using an infusion pump over 0.3-2 hours. Intravenous drip can be repeated 2-3 times within 24 hours. The rate of drug administration is adjusted depending on the clinical effect

The therapeutic effect appears within the first minutes of administration and gradually decreases after the infusion is stopped, therefore, if it is necessary to continue treatment with Amiodarone, it is recommended to switch to a constant intravenous drip of the drug.

Maintenance 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, a gradual transition to taking the drug inside (3 tablets of 200 mg per day) should begin. The dose may be increased to 4 or even 5 tablets per day.

Intravenous jet administration

Intravenous bolus administration is usually not recommended due to the risk of hemodynamic complications (a sharp decrease in blood pressure and collapse are possible).

Intravenous bolus injection should be carried out only in urgent cases with the 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. Except in cases of cardioresuscitation in defibrillation-resistant ventricular fibrillation, intravenous bolus administration of Amiodarone should be carried out for at least 3 minutes. Re-introduction of the drug should not be carried out earlier than 15 minutes after the first injection, even if the contents of only one ampoule were initially administered (possibility of irreversible collapse).

If there is a need to continue the administration of the drug Amiodarone, it should be administered as an infusion.

Cardiac resuscitation in cardiac arrest caused by defibrillation-resistant ventricular fibrillation

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

If fibrillation is not stopped, additional intravenous jet administration of Amiodarone at a dose of 150 mg (or 2.5 mg/kg of body weight) to a concentration of 7.5 mg/ml is possible.

Do not mix in the same syringe with other drugs!

Overdose

There is no information on overdose of amiodarone (concentrate for solution for intravenous administration). Several cases have been described acute overdose amiodarone, taken orally, manifested by sinus bradycardia, polymorphic ventricular tachycardia of the "pirouette" type, cardiac arrest, circulatory disorders and liver function, a pronounced decrease in blood pressure.

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

Precautionary measures

Intravenous bolus injection of amiodarone is usually not recommended due to hemodynamic risks (development of a pronounced decrease in blood pressure, vascular collapse), intravenous drip administration of the drug is preferred.

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

In order to avoid the occurrence of reactions at the injection site, Amiodarone is recommended to be administered through a central venous catheter. Only in the case of cardioresuscitation during cardiac arrest caused by defibrillation-resistant ventricular fibrillation, in the absence of central venous access (no central venous catheter installed), Amiodarone can be administered into a large peripheral vein with maximum blood flow. If it is necessary to continue treatment with Amiodarone after cardiac resuscitation, Amiodarone should be administered intravenously through a central venous catheter under constant monitoring of blood pressure and ECG.

Amiodarone should not be mixed in the same syringe or dropper with other medicines. Do not inject other drugs into the same infusion line as Amiodarone.

Reactions from the heart

New arrhythmias or worsening of existing arrhythmias have been reported, sometimes fatal. It is very important to make a differential diagnosis between the lack of efficacy of the drug and its arrhythmogenic effect, combined or not with an aggravation of the severity. cardiovascular pathology. With the use of the drug Amiodarone, arrhythmogenic effects were reported much less frequently than with other antiarrhythmic drugs and, as a rule, it was observed in the presence of factors that increase the duration of the QT interval, such as interaction with other drugs and / or electrolyte disturbances in the blood. Despite the ability of the drug Amiodarone to increase the duration of the QT interval, it showed low activity in terms of provoking polymorphic ventricular tachycardia of the "pirouette" type.

Severe bradycardia.

When using Amiodarone in combination with sofosbuvir in combination with other direct-acting antiviral drugs against viral hepatitis C, such as daclatasvir, simeprevir, ledipasvir, there have been cases of severe, potentially life-threatening, bradycardia, as well as heart block. Therefore, the simultaneous use of these drugs with Amiodarone is not recommended.

If the concomitant use of these drugs with Amiodarone cannot be avoided, careful monitoring of patients is recommended after starting sofosbuvir in combination with other direct-acting antiviral drugs. After the start of the simultaneous use of sofosbuvir, patients who are at high risk of developing bradyarrhythmia should be continuously observed 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 have discontinued amiodarone within the last few months before starting treatment with sofosbuvir in combination with other direct-acting antivirals.

Patients taking the above drugs for hepatitis C virus in combination with Amiodarone, both simultaneously with other drugs that slow the heart rate, and without combination with such drugs, should be informed about symptoms that indicate the development of bradycardia and heart block. If they occur, they should immediately seek medical attention.

Pulmonary disorders

The appearance of shortness of breath 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 interstitial development is suspected

Bibliography:

1. Anatomical Therapeutic Chemical Classification (ATX);
2. Nosological classification (ICD-10);
3. Official instruction from the manufacturer.

Prices for amiodarone in pharmacies in Moscow

Release form: Amiodarone 200mg 30 pcs. tablets

Release form: Amiodarone 200mg 30 pcs. tablets

Release form: Amiodarone 200mg 30 pcs. tablets

Release form: Amiodarone 50mg/ml 3ml 10 pcs. concentrate for solution for intravenous administration

Release form: Amiodarone 200mg 30 pcs. tablets