Amiodarone instructions for use in ampoules. Cordarone for injection - instructions for use

• Latin name:Amiodaron
• ATX Code:C01BD01
• Active substance:Amiodarone (Amiodarone)
• Manufacturer:Balkanpharma-Dupnitza (Bulgaria), North Star, Organics, Biocom CJSC, AVVA-RUS, Obolenskoye FP (Russia)

Composition

Amiodarone contains 200 mg per tablet. amiodarone hydrochloride and excipients such as: lactose, corn starch, alginic acid, low molecular weight povidone and magnesium stearate.

Release form

Amiodarone is available in tablets in blisters of 10 pieces or in a jar of light-protective glass of 30 pieces. The drug is packaged in cardboard packs that can hold 30 or 60 tablets.

Solution for intravenous administration (recipe for latin language): Rp .: Sol. 300 mg Amiodaroni diluitur Dextrosum 5% - 20 ml.

pharmachologic effect

It has antiarrhythmic, coronary azodilating and antianginal effects.

Pharmacodynamics and pharmacokinetics

Amiodarone — active substance, which is able to facilitate the work of the heart without significantly changing cardiac output and contractility of the heart muscle myocardium . At the same time, the drug increases coronary blood flow by reducing resistance in the arteries of the heart, and also reduces heart rate and blood pressure due to peripheral vasodilating effect . This significantly reduces the level of oxygen consumption by the myocardium and at the same time increases the energy reserves of the myocardium by increasing the content creatine phosphate and glycogen .

Indications for use Amiodarone

It is used for treatment as well as prevention paroxysmal rhythm disturbances :

• ventricular that threaten life as well as in patients with myocarditis of Chagas ;
• ventricular ;
• prevention ventricular fibrillation , inter alia, after events cardioversion ;
• flickering paroxysm ;
• atrial flutter ;
• extrasystole atrial or ventricular ;
• arrhythmias arising from the background chronic heart or coronary insufficiency ;
• parasystole ;

Indications for the use of Amiodarone are also supraventricular arrhythmias in cases of ineffectiveness or inability to use any other therapy, which is usually associated with WPW syndrome.

Contraindications

• sinus bradycardia ;
• weak sinus syndrome ;
• sinoatrial or 2nd and 3rd degree (without application pacemaker );
• cardiogenic shock ;
• collapse ;
• hypokalemia ;
• arterial hypotension ;
• (insufficient secretion of thyroid hormones);
• interstitial lung diseases ;
• the reception mAO inhibitors ;
• period and;
• hypersensitivity to Amiodarone components or to;
• with caution should be used in children and adolescents under 18 years of age.

Side effects

The use of Amiodarone tablets can cause the following side effects regarding certain organs and systems:

• The cardiovascular system: sinus bradycardia (refractory to m-anticholinergics ), AV block , vasculitis with prolonged use - progression of heart failure , ventricular arrhythmia type " pirouette ", Strengthening the existing arrhythmias or its occurrence, with parenteral use - decrease in blood pressure .
• Endocrine system: developing hypo - or hyperthyroidism .
• Respiratory system: prolonged use may result in coughing , interstitial pneumonia or as well pulmonary fibrosis , pleurisy. With parenteral administration, possible bronchospasm , especially in people with severe forms of respiratory failure.
• Digestive system: most often occurs nausea , vomiting , or, severity in epigastric , decreases, taste sensations become dull, less often - increased activity liver transaminase in case of prolonged use - toxic hepatitis , cholestasis , icteric staining , and .
• Central and peripheral nervous system: possible asthenia auditory. In case of prolonged use - peripheral neuropathy extrapyramidal manifestations, impaired memory, sleep, ataxia , neuritis optic nerve . With parenteral administration, it may develop intracranial hypertension .
• Sensory organs: uveitis (inflammation choroid eyes of various localization), deposition glycolipoprotein — lipofuscin in cornea eyes , which can manifest itself in bright light in the form of violations: complaints of luminous dots or the so-called “veil before the eyes”, in addition, it is possible retinal microbleaching .
• Hematopoietic organs: thrombocytopenia , hemolytic or aplastic anemia .
• Skin integument: rash defeat in the form exfoliative , photosensitization , rarely there were manifestations in the form of gray-blue staining of the skin.
• Other: epididymitis and decline, myopathy with parenteral administration is possible and increased sweating .

The use of the drug in elderly patients significantly increases the risk of developing severe forms bradycardia .

Amiodarone tablets, instructions for use (method and dosage)

Amiodarone tablets should be taken orally, before meals, with the necessary amount of water to be swallowed. Instructions for use Amiodarone involves an individual dosage regimen, which should be established and adjusted by the attending physician.

Standard dosing schedule:

• Loading (otherwise saturating) initial dose for inpatient treatment, which is divided into several doses, is 600-800 mg per day, and the maximum allowable daily dose is up to 1200 mg. It must be borne in mind that the total dose should be 10 g, usually it is reached in 5-8 days.
• For outpatient treatment prescribe an initial dose in the range of 600-800 mg per day, which is divided into several doses, reaching the total dose of not more than 10 g, but in 10-14 days.
• To continue the course of treatment with Amiodarone, it is enough to take 100-400 mg per day. Attention! The minimum effective maintenance dose is used.
• To avoid cumulation of the drug, it is necessary to take tablets either every other day, or with an interval of 2 days 1 time per week.
• The average single dose with therapeutic effectis 200 mg.
• The average daily dose is 400 mg.
• The maximum allowable dose is not more than 400 mg per 1 time, not more than 1200 mg per 1 knock.
• For children, the dose is usually in the range of 2.5-10 mg per day.

Overdose

A significant single dose may cause:

• decrease;
• bradycardia or ;
• violation of the normal functioning of the liver;
• atrioventricular block .

As a treatment prescribed gastric lavage , symptomatic measures, with development bradycardia — , β1-adrenergic agonists in extreme cases - pacing .

Specific does not exist, turns out to be ineffective.

Interaction

With the simultaneous use of this drug with the following agents, various reactions may occur:

• Class 1A antiarrhythmic drugs and Disopyramids , Procainamide , Quinidine increase the cardiac QT interval and increase the risk of developing pirouette ventricular tachycardia.
• Laxatives hypokalemia , and diuretics , corticosteroids including in / in Tetracosactide in combination with Amiodarone increase the risk of ventricular arrhythmias.
• General means anesthesia , oxygen therapy - the risk of developing bradycardia, cardiac conduction disturbances, arterial hypotension, and a decrease in V heart shock.
• Tricyclic antidepressants, phenothiazines , Astemizole and

Description

Transparent liquid with a yellowish or greenish tint.

Composition

One ampoule (3 ml of solution) contains: active substance: amiodarone hydrochloride - 150 mg; excipients: sodium acetate trihydrate, glacial acetic acid, polysorbate 80, benzyl alcohol, water for injection.

Pharmacotherapeutic group

Means for the treatment of heart disease. Antiarrhythmic drugs, class III.
ATX Code:C01BD01.

Pharmacological properties"type \u003d" checkbox "\u003e

Pharmacological properties

Pharmacodynamics
Antiarrhythmic properties
Elongation of phase 3 of the action potential of cardiomyocytes without changing its height or ascent rate (class III according to the classification of Vaughan-Williams). An isolated extension of the 3 phase action potential occurs due to the slowdown of potassium currents, without changing the currents of sodium or calcium.
Bradycardia effect by reducing the automatism of the sinus node. This effect not eliminated by the administration of atropine.
Non-competitive inhibitory effect on alpha and beta adrenergic receptors, without their complete blockade.
Slowing of sinoatrial, atrial and atrioventricular conduction, which is more pronounced against the background of tachycardia.
Does not alter intraventricular conduction.
It increases the refractory period and reduces myocardial excitability at the sinoatrial, atrial and atrioventricular levels.
Slows down the conductivity and lengthens the refractory period of the extra atrial ventricular pathways.
It does not have a negative inotropic effect.
Pharmacokinetics
The amount of parenterally administered amiodarone in the blood decreases very rapidly due to tissue saturation with the drug and its binding sites; the action reaches a maximum 15 minutes after administration and disappears after about 4 hours.
To achieve tissue saturation, it is necessary to continue intravenous or oral administration. During saturation, amiodarone accumulates, especially in adipose tissue, and an equilibrium state is achieved over a period of one to several months.
Amiodarone hydrochloride has a long half-life, which is from 20 to 100 days. The main route of excretion is through the liver with bile; 10% of the substance is excreted by the kidneys. Due to the low renal elimination, Amiodarone can be administered to patients with renal failure without dose adjustment.

Indications for use

Drug treatment should begin in a hospital and under the supervision of a specialist. The drug is intended only for the treatment of severe rhythm disturbances that do not respond to other treatments, or when other treatments cannot be used.
Tachyarrhythmias associated with Wolf-Parkinson-White syndrome.
Tachyarrhythmias of all types, including supraventricular, nodular and ventricular tachycardia; atrial flutter and fibrillation, ventricular fibrillation; in case when other medicines cannot be used.
The drug can be used when a quick response to treatment is required or when oral administration is not possible.

Contraindications

- Sinus node weakness syndrome (SSS), sinus bradycardia, sinoatrial blockade, with the exception of cases of correction by an artificial pacemaker;
- atrioventricular block II and III degreeViolations of intraventricular conduction (blockade of two and three legs of the bundle of His); in these cases, the drug can be used in specialized departments under the guise of an artificial pacemaker (pacemaker);
- cardiogenic shock, collapse;
- severe arterial hypotension;
- simultaneous use with medicinescapable of causing polymorphic ventricular tachycardia of the pirouette type;
- thyroid dysfunction (hypothyroidism, hyperthyroidism);
- hypokalemia;
- pregnancy;
– breast-feeding;
– hypersensitivity to iodine and / or amiodarone;
- Severe pulmonary dysfunction (interstitial lung disease);
- cardiomyopathy or decompensated heart failure (possibly worsening the patient's condition).
Due to the presence of benzyl alcohol, Amiodarone is contraindicated in newborns, infants and children under 3 years of age.

Dosage and administration

Method of application - intravenous.
Do not dilute the drug with isotonic sodium chloride solution, as precipitate formation is possible!
Do not mix with other drugs in the same infusion system.
The drug should be used only when there is necessary equipment for monitoring cardiac function, defibrillation and pacemaker.
The drug can be used before cardioversion with direct current.
The standard recommended dose is 5 mg / kg body weight, which is administered by infusion over a period of time from 20 minutes to 2 hours. The drug can be administered in the form of a solution diluted in 250 ml of a 5% glucose solution. After this, repeated infusion of the drug in a dose of up to 1200 mg (approximately 15 mg / kg body weight) in a 5% glucose solution up to 500 ml in volume for 24 hours can be applied, while the infusion rate must be adjusted depending on the clinical response of the patient ( see the Precautions section).
In extremely urgent clinical situations, the medicine, at the discretion of the doctor, can be administered as a slow injection at a dose of 150-300 mg in 10-20 ml of 5% glucose solution for at least 3 minutes. After this, the repeated administration of the drug can be carried out no earlier than 15 minutes. Patients who are given the drug as described above should be closely monitored, for example, in the intensive care unit (see the "Precautions" section).
Transition from intravenous to oral administration
Immediately after receiving the appropriate response to treatment, you must simultaneously begin oral therapy the drug in the usual loading dose (i.e. 200 mg three times a day). After this, the drug should be gradually withdrawn by incremental dose reduction.
Children
The safety and effectiveness of amiodarone in children have not been evaluated, therefore the use of this drug in children is not recommended. The drug contains benzyl alcohol. There are reports of deaths resulting from the development of "dyspnea syndrome" ("gasping syndrome") in newborns after administration of solutions containing this preservative. Symptoms of this complication include the sudden onset of shortness of breath, arterial hypotension, bradycardia, and the development of cardiovascular collapse.
Elderly patients
As with other patients, it is important to use the minimum effective dose of the drug. Although there is no evidence in favor of specific drug dosage requirements in this group of patients, these patients may be more likely to develop bradycardia and conduction disturbances when using too high a dose. Particular attention should be paid to monitoring thyroid function (see sections "Contraindications", "Precautions" and "Undesirable reactions").
Patients with renal and / or liver failure
Although dosage adjustments are made for patients with renal or hepatic impairment during prolonged oral administration Amiodarone was not required, careful clinical monitoring of patients of this category, especially the elderly, in the intensive care unit is necessary.
Cardiopulmonary resuscitation
The recommended dose for ventricular / ventricular tachycardia fibrillation with no pulse, defibrillation-resistant, is 300 mg (or 5 mg / kg body weight), which is administered diluted in 20 ml of 5% glucose solution by rapid injection. If ventricular fibrillation persists, an additional 150 mg (or 2.5 mg / kg body weight) of the drug can be used.

Side effects"type \u003d" checkbox "\u003e

Side effects

Adverse reactions classified according to classes of organ systems and frequency of occurrence in accordance with the following criteria: very often (\u003e 1/10); often (\u003e 1/100 to< 1/10); нечасто (> 1/1000 to< 1/100); редко (> 1/10000 to< 1/1000); очень редко (< 1/10000); неизвестно (не может быть оценена на основе имеющихся данных).
Violations of the blood and lymphatic system.In patients taking amiodarone, bone marrow granulomas were detected. The clinical significance of these findings is unknown.
Violations of the heart. Often: bradycardia. Rarely: the occurrence of a new or worsening of the course of existing arrhythmia, sometimes followed by cardiac arrest. Severe bradycardia, sinus block, which requires the abolition of amiodarone, especially in patients with sinus node dysfunction and / or elderly patients, is paroxysmal ventricular tachycardia such as "torsade de pointes". Conductivity disorders (sinoatrial block, AV block).
Endocrine Disorders Seldom:hyperthyroidism (see section "Precautions"). Rarely: syndrome of inadequate secretion of antidiuretic hormone (SIADH). Unknown: hypothyroidism.
Violations of the gastrointestinal tract. Often:nausea. Unknown: pancreatitis (acute).
Violations of the liver and biliary tract. Rare: moderate and isolated rise the level of transaminases (1.5–3 times higher than the norm) at the beginning of treatment, which disappeared after discontinuation of the drug or even spontaneously; acute liver damage with an increase in serum transaminases and / or jaundice, including liver failure, sometimes fatal (see section "Precautions").
General disorders and reactions at the injection site. Often:an inflammatory reaction is possible, in particular phlebitis of superficial veins, if injected directly into the peripheral vein; reactions at the injection site, in particular pain, erythema, edema, necrosis, extravasation, formation of infiltrate, inflammation, skin induction, thrombophlebitis, cellulitis, infections and pigmentation disorders. Rarely: benzyl alcohol adjuvant may cause hypersensitivity reactions.
Violations by the immune system. Seldom:hypersensitivity reactions, including anaphylactic shock. Unknown:cases of angioedema have been reported (Quincke's edema).
Violations of the muscular, skeletal and connective tissue. Unknown: backache.
Violations by nervous system. Often:extrapyramidal tremor. Infrequently: peripheral sensorimotor neuropathy and / or myopathy, usually reversible. Seldom: benign intracranial hypertension (pseudotumor of the brain), headache.
Disorders from the respiratory system, organs chest and mediastinum. Seldom:acute respiratory distress syndrome, in some cases with a fatal outcome (see section "Precautions"), bronchospasm and / or apnea in case of severe respiratory failure, especially in patients with bronchial asthmainterstitial pneumonia.
Violations of the skin and subcutaneous tissues. Often:eczema. Redto: excessive sweating. Unknown: urticaria, skin reactions such as toxic epidermal necrolysis (TEN) / Stevens-Johnson syndrome, bullous dermatitis, and a drug reaction with eosinophilia and systematic symptoms.
Violations of the organ of vision. Often: microdeposits on the anterior surface of the cornea, located on the site below the pupil, are found in almost every patient. Cause colored halos in blinding light or blurred vision. They usually regress 6-12 months after stopping amiodarone hydrochloride. Rarely: optical neuropathy / neuritis, which can progress to blindness.
Violations of the vessels. Often: usually moderate and short-term decline blood pressure. There have been reports of cases of severe arterial hypotension or vascular collapse, in particular in case of overdose or after very rapid administration. Seldom:the tides.

Interaction with other drugs

Precautions

Excipients
The drug contains benzyl alcohol, which can cause toxic and allergic reactions in infants and children under the age of 3 years (see section "Dosage and administration").
Since benzyl alcohol crosses the placenta, injection solutions containing benzyl alcohol are not recommended during pregnancy.
Central vein infusion
With the exception of emergency situations, Amiodarone should be used only in specialized intensive care units, subject to constant monitoring (ECG, blood pressure).
The drug should be administered through the central veins, since administration through the peripheral veins can cause local reactions.
The drug must be administered only in the form of an infusion, since even a very slow injection can enhance the manifestations of arterial hypotension, heart failure or severe respiratory failure (see section "Adverse reactions").
If it is impossible to introduce into the central vein, the drug can be administered through peripheral veins with maximum blood flow.
Heart symptoms
There have been cases of occurrence or exacerbation of existing arrhythmias, sometimes fatal (see section "Adverse reactions"). The arrhythmogenic effect of amiodarone is weak or less pronounced than the arrhythmogenic effect of most antiarrhythmic drugs, and usually manifests itself when certain combinations of drugs are used (see the “Interaction with Other Medicines” section) or in violation electrolyte balance.
Pulmonary symptoms
Several cases of interstitial pneumopathy have been reported with the use of the drug. The appearance of shortness of breath or dry cough, both separately and against a background of worsening general condition, indicates the possibility of pulmonary toxicity, such as interstitial pneumopathy, and requires monitoring of the patient's condition (see section "Adverse reactions"). It is necessary to reconsider the feasibility of using amiodarone, since interstitial pneumopathy is usually reversible if amiodarone is withdrawn early.
In addition, in some patients treated with amiodarone, there were cases of acute respiratory distress syndrome immediately after surgery, therefore, with mechanical ventilation, it is recommended to carefully monitor the condition of such patients.
Thyroid disease
Amiodarone can cause hyperthyroidism, especially in patients with a history of thyroid disease or taking / previously taking amiodarone. The diagnosis is confirmed by a pronounced decrease in the level of thyroid-stimulating hormone (TSH).
Amiodarone contains iodine and therefore may affect the reception of radioiodine. However, the results of a thyroid function test (free T3, free T4, TSH) remain interpretable. Amiodarone inhibits the peripheral conversion of thyroxine (T4) and triiodothyronine (T3) and can cause local biochemical changes in patients with normal thyroid function (an increase in the level of free T4 against the background of a slight decrease or even the normal level of free T3). Such phenomena do not require cancellation of treatment with amiodarone.
Hepatic symptoms
Severe and sometimes fatal hepatocellular insufficiency may develop within 24 hours after the start of the use of the drug. At the beginning of treatment and further throughout the course of treatment with amiodarone, regular monitoring of liver function is recommended (see section "Adverse reactions"). It is necessary to reduce the dose of amiodarone or to discontinue this drug if the level of transaminases has grown more than three times in comparison with the normal values \u200b\u200bof these indicators.
Electrolyte imbalance
It is important to consider situations that may be associated with hypokalemia and can provoke proarrhythmogenic effects. Hypokalemia should be eliminated before use of amiodarone.
Anesthesia
Before surgery inform the anesthetist that the patient is receiving amiodarone. Long-term treatment with amiodarone may increase the risk of developing hemodynamic side effectsassociated with general or local anesthesia, such as: bradycardia, arterial hypotension, decreased cardiac output, and impaired conduction.
Disorders associated with interactions with other drugs
Joint use with beta-adrenoreceptor blockers, except sotalol (a contraindicated combination) and esmolol (a combination that requires caution in use); verapamil and diltiazem can be used only in case of prevention of ventricular arrhythmias that are life-threatening (see the section "Interaction with other drugs").

Dosage form

clear liquid with a yellowish or greenish tint.

Composition

each ampoule (3 ml of solution) contains: active substance: amiodarone hydrochloride - 150 mg; excipients: sodium acetate trihydrate, glacial acetic acid, polysorbate 80, benzyl alcohol, water for injection.

Pharmacodynamics

Antiarrhythmic properties:

Elongation of phase 3 of the action potential of cardiomyocytes without changing its height or rate of rise (class III according to the classification of Vaughan Williams). An isolated extension of the 3 phase action potential occurs due to the slowdown of potassium currents, without changing the currents of sodium or calcium.

Bradycardia effect by reducing the automatism of the sinus node. This effect is not eliminated by the administration of atropine.

Non-competitive inhibitory effect on alpha and beta adrenergic receptors, without their complete blockade.

Slowing of sinoatrial, atrial and atrioventricular conduction, which is more pronounced against the background of tachycardia.

Does not alter intraventricular conduction.

It increases the refractory period and reduces myocardial excitability at the sinoatrial, atrial and atrioventricular levels.

Slows down conduction and lengthens the refractory period of additional atrioventricular pathways.

It does not have a negative inotropic effect.

Pharmacokinetics

The amount of parenterally administered amiodarone in the blood decreases very rapidly due to tissue saturation with the drug and its binding sites; the action reaches a maximum 15 minutes after administration and disappears after about 4 hours.

Side effects

The frequency of adverse reactions:

Very often -\u003e 10%;

Infrequently -\u003e 1%,<10%;

Rarely -\u003e 0.1%,<1%;

Very rarely\u003e 0.01%<0,1%;

The frequency cannot be determined on the basis of available data -<0,01% и менее.

From the cardiovascular system: very often: bradycardia; infrequently - severe bradycardia; seldom - a stop of a sinus node, were noted in some cases, especially at elderly patients, proaritmogenic action.

From the digestive system: often: nausea.

Local reactions at the injection site: very often: inflammatory reactions (superficial phlebitis) are possible when injected directly into the peripheral vein, reactions at the injection site, such as pain, erythema, edema, necrosis, transudation, infiltration, inflammation, phlebitis and cellulite.

From the liver: there are reports of cases of impaired liver function; these cases were diagnosed by elevated serum transaminases. The following was noted:

Very rarely: usually a moderate and isolated increase in the level of transaminases (1.5-3 times higher than normal), disappearing after a dose reduction and even spontaneously; acute hepatitis (several isolated cases) with an increase in the level of transaminases in the blood and / or jaundice, sometimes with a fatal outcome; withdrawal of treatment is required; chronic hepatitis with prolonged treatment (inside). The histological picture corresponds to pseudo-alcoholic hepatitis. Since the clinical and laboratory picture of the disease is very heterogeneous (passing hepatomegaly, an increase in the level of transaminases in 1.5 - 5 times above normal), regular monitoring of liver function is required. Even with a moderate increase in the level of transaminases in the blood observed after treatment lasting more than 6 months, chronic impairment of liver function should be suspected. Clinical abnormalities and laboratory abnormalities usually disappear after discontinuation of the drug. Several cases of irreversible progression have been noted.

From the immune system: very rarely: anaphylactic shock.

From the side of the nervous system: very rarely: benign intracranial hypertension (pseudotumor of the brain).

From the respiratory system: very rarely, several cases of acute respiratory distress syndrome were observed, mainly associated with interstitial pneumonitis, sometimes fatal and sometimes immediately after surgery (it is possible to interact with high doses of oxygen during mechanical ventilation). Consideration should be given to withdrawing amiodarone and the advisability of administering corticosteroids; bronchospasm and / or apnea in severe respiratory failure, especially in patients with bronchial asthma.

On the part of the skin, subcutaneous tissue: very rarely sweating, hair loss.

From the vascular system: very often - usually a moderate and transient drop in blood pressure. Cases of severe hypotension or circulatory shock are described, especially after overdose or due to too rapid administration.

Very rare: hot flashes.

Sale Features

prescription

Special conditions

Precautions

Disorders of electrolyte metabolism, especially hypokalemia: it is important to take into account situations that may be accompanied by hypokalemia, as predisposing to proarrhythmic phenomena. Hypokalemia must be corrected before amiodarone is given.

Except in cases of emergency therapy, Amiodarone in the form of a solution for intravenous injection can be used only in a hospital and with constant monitoring (ECG, blood pressure).

Used with caution in chronic heart failure, liver failure, bronchial asthma, in old age.

Anesthesia

Before surgery, the anesthetist should be informed that the patient is receiving amiodarone.

Prolonged treatment with amiodarone may increase the hemodynamic risk inherent in local or general anesthesia (may cause bradycardia, hypotension, decreased cardiac output, or impaired conduction).

Combinations (see Interactions with other drugs and other forms of interaction) with beta-blockers other than sotalol (a contraindicated combination) and esmolol (a combination that requires special care when used), verapamil and diltiazem, can only be considered in the context of the prevention of life-threatening ventricular arrhythmias and in case of cardiopulmonary resuscitation during cardiac arrest caused by refractory ventricular fibrillation.

Pregnancy and breastfeeding

Animal tests did not reveal the teratogenic effect of Amiodarone. Therefore, one should not expect malformations in humans, since it has been shown that drug-causing malformations exhibit teratogenic effects in animals in correctly conducted experiments on two different animal species.

In clinical practice, the currently available information is insufficient to assess whether amiodarone causes malformations when used in the first trimester of pregnancy. Since the thyroid gland of the fetus begins to bind iodine only from the 14th week of pregnancy, the drug is not expected to affect it in case of earlier use. An excess of iodine when using the drug after this period can lead to laboratory signs of hypothyroidism in the fetus or even to clinical goiter.

The drug is contraindicated since the second trimester of pregnancy.

Amiodarone, its metabolite and iodine are excreted in breast milk in concentrations exceeding the level in maternal plasma. If the mother receives treatment with this drug, breast-feeding is contraindicated in connection with the danger of developing hypothyroidism in the child.

Influence on the ability to drive vehicles and control mechanisms

Currently, there is no evidence that amiodarone affects the ability to drive vehicles and control mechanisms.

Overdose

Symptoms: sinus bradycardia, cardiac arrest, paroxysmal ventricular tachycardia, ventricular tachycardia of the pirouette type, circulatory disorders, impaired liver function, decreased blood pressure.

Treatment: symptomatic therapy is carried out (with bradycardia - beta-adrenostimulants or the installation of a pacemaker, with tachycardia of the “pirouette” type - intravenous administration of magnesium salts, reducing cardiac pacing) Amiodarone and its metabolites are not removed during hemodialysis and peritoneal dialysis.

Indications

Treatment of severe cardiac arrhythmias in cases where oral administration is not possible, namely:

Atrial rhythm disturbances with a high frequency of ventricular contractions;

Tachycardia associated with Wolf-Parkinson-White syndrome;

Documented symptomatic, life-threatening, leading to disability ventricular rhythm disturbances;

Cardiopulmonary resuscitation in cardiac arrest caused by refractory ventricular fibrillation.

Contraindications

- SSSU, sinus bradycardia, sinoatrial blockade, with the exception of cases of correction by an artificial pacemaker;

- atrioventricular block II and III degree, disturbances of intraventricular conduction (blockade of two and three legs of the bundle of His); in these cases, amiodarone intravenously can be used in specialized departments under the guise of an artificial pacemaker (pacemaker);

- cardiogenic shock, collapse;

- severe arterial hypotension;

- simultaneous use with drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type;

- thyroid dysfunction (hypothyroidism, hyperthyroidism);

- hypokalemia;

- pregnancy;

- breast-feeding;

- Hypersensitivity to iodine and / or amiodarone;

- Severe pulmonary dysfunction (interstitial lung disease);

- cardiomyopathy or decompensated heart failure (possibly worsening the patient's condition).

Due to the presence of benzyl alcohol, intravenous administration of amiodarone is contraindicated in newborns, infants and children under 3 years of age.

Dosage and administration

Due to the peculiarities of the dosage form of the drug, a concentration of less than 2 ampoules per 500 ml cannot be used; only an isotonic glucose solution is used. Do not add other drugs to the infusion solution.

Amiodarone should be injected into the central vein, except in cases of cardiopulmonary resuscitation during cardiac arrest, when peripheral veins can be used in the absence of central venous access (see "Precautions").

It is prescribed for severe arrhythmias, in which the use of oral drugs is impossible, with the exception of cardiopulmonary resuscitation during cardiac arrest caused by refractory ventricular fibrillation.

Central vein infusion

Initial dose: usually 5 mg / kg, in glucose solution (if possible with the use of an infusomat), within 20 minutes to 2 hours; the infusion can be repeated 2-3 times within 24 hours. Short-term action of the drug requires continued administration.

Maintenance treatment: 10-20 mg / kg per day (an average of 600-800 mg / day and up to 1200 mg / day) in 250 ml of glucose solution for several days. From the first day of infusion, a gradual transition to oral administration begins (3 tablets per day). The dose can be increased to 4 or even 5 tablets per day.

Infusion into the peripheral vein under conditions of cardiopulmonary resuscitation during cardiac arrest caused by ventricular fibrillation, refractory to electrical defibrillation.

Taking into account the method of application and in view of the situation in which this indication occurs, it is recommended to use a central venous catheter, if available; otherwise, the drug can be injected into the largest peripheral vein.

Drug interaction

Medicines that can cause ventricular tachycardia of the pirouette type are primarily antiarrhythmic drugs of Ia and III class and some antipsychotics. Hypokalemia is a predisposing factor, as is bradycardia or congenital or acquired lengthening of the QT interval.

Combination with

Drugs that can cause ventricular tachycardia of the pirouette type.

Class Ia antiarrhythmic drugs (quinidine, hydroquinidine, isopyramides).

Class III antiarrhythmic drugs (dofetilide, ibutilide, sotalol).

Other drugs, such as bepridil, cisapride, difemanil, iv rithromycin, misolastine, iv vincamine, moxifloxacin, iv spiramycin.

Sulopridom.

These contraindications do not apply to the use of amiodarone for cardiopulmonary resuscitation in case of cardiac arrest resistant to electrical defibrillation.

Cyclosporine

It is possible to increase the level of cyclosporine in plasma, associated with a decrease in the metabolism of the drug in the liver, with possible nephrotoxic manifestations.

Determination of the level of cyclosporine in the blood, checking kidney function and reviewing the dosage during treatment with amiodarone and after discontinuation of the drug.

Diltiazem for injection

Verapamil for injection

The risk of bradycardia and atrioventricular block. If a combination is unavoidable, it is necessary to establish strict clinical and continuous ECG monitoring.

If a combination is unavoidable, preliminary monitoring of the QT interval and ECG monitoring are necessary.

Antipsychotics that can cause ventricular tachycardia of the pirouette type:

Some phenothiazine antipsychotics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazin), benzamides (amisulpride, sulpiride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), and other antipsychotics (p.

The risk of ventricular rhythm disturbances (pirouette type tachycardia) increases.

The risk of ventricular rhythm disturbances (pirouette type tachycardia) increases. Recommended: ECG and clinical observation.

Combinations requiring precautions when using Amiodarone with:

Oral anticoagulants:

Strengthening the anticoagulant effect and the risk of bleeding, due to an increase in the concentration of anticoagulants in the plasma. The need for more frequent monitoring of the level of prothrombin in the blood and MHO (INR), as well as the adaptation of doses of anticoagulants during treatment with amiodarone and after discontinuation of the drug.

Beta-blockers, with the exception of sotalol (a contraindicated combination) and esmolol (a combination requiring caution in use)

Beta-blockers prescribed for heart failure (bisoprolol, carvedilol, metoprolol)

Violations of contractility and conduction (synergistic effect) with a risk of developing severe bradycardia. Increased risk of ventricular arrhythmias, especially pirouette type tachycardia.

Regular clinical and electrocardiographic monitoring is required.

Cardiac glycosides

Disorders of automatism (excessive bradycardia) and atrioventricular conduction (synergy of action). When using digoxin, an increase in its concentration in plasma (due to a decrease in alkaloid clearance).

It is necessary to carry out clinical and ECG monitoring, as well as determining the level of digoxin in plasma); it may be necessary to change the dose of digoxin.

Diltiazem for oral administration

Verapamil for oral administration

The risk of bradycardia and atrioventricular block, especially in the elderly. Clinical and ECG monitoring.

Esmolol

Violations of contractility, automatism and conduction (suppression of compensatory sympathetic mechanisms). Clinical and ECG monitoring.

Hypokalemic drugs: potassium-excreting diuretics (in monotherapy or in combination), stimulant laxatives, amphotericin B (iv) glucocorticoids (systemic), tetracosactide.

The risk of ventricular rhythm disturbances, in particular tachycardia of the pirouette type, increases (hypokalemia is a predisposing factor). Clinical and ECG monitoring, laboratory tests.

Lidocaine

The risk of an increase in plasma concentration of lidocaine, with the likelihood of neurological and cardiological side effects, due to a decrease in amiodarone metabolism of lidocaine in the liver. Clinical and ECG control, if necessary, dose adjustment of lidocaine during treatment with amiodarone and after its cancellation.

Orlistat

The risk of a decrease in the concentration of amiodarone and its active metabolite in plasma. Clinical and, if necessary, ECG monitoring,

Phenytoin (and, by extrapolation, phosphenytoin)

An increase in plasma phenytoin levels with symptoms of an overdose, especially of a neurological nature (decreased phenytoin metabolism in the liver). Clinical monitoring and determination of plasma phenytoin levels; if possible, a reduction in the dose of phenytoin.

Simvastatin

Increased risk of side effects (dose-dependent) such as rhabdomyolysis (decreased metabolism of simvastatin in the liver). The dose of simvastatin should not exceed 20 mg per day.

If at this dose the therapeutic effect cannot be achieved, you should switch to another statin that does not enter into interactions of this type.

Tacrolimus

An increase in the level of tacrolimus in the blood due to the inhibition of its metabolism by amiodarone. It is necessary to measure the level of tacrolimus in the blood, monitor the functioning of the kidneys and level the level of tacrolimus.

Drugs that cause bradycardia:

Many drugs can cause bradycardia. This is especially true for class Ia antiarrhythmic drugs, beta blockers, some class III antiarrhythmic drugs, some calcium channel blockers, digitalis preparations, pilocarpine, and anticholinesterase agents.

The risk of excessive bradycardia (cumulative effect).

Combinations to consider

Bradycardia-causing drugs: calcium channel blockers with a bradycardic effect (verapamil), beta-blockers (except sotalol), clonidine, guanfacine, digitalis alkaloids, mefloquine, cholinesterase inhibitors (donezepil, galantamine, trivinigmine, pirminiginmine, pirminigidmine, pirminigidmine, pirminigidmine, pirminigidmine, pirminigidmine, pirminigidmine, pirminigidmine, pirminigidmine, pirminigidmine, pirminigi pilocarpine.

The risk of excessive bradycardia (cumulative effects).

Incompatibilities

When using PVC material or medical equipment plasticized with 2-diethylhexylphthalate (DEHP) in the presence of an amiodarone injection solution, DEHP can be released. For minimal exposure to DEHP, it is recommended that the final dilution of the solution be made before infusion in equipment that does not contain DEHP.

C.01.B.D.01 Amiodarone