Instructions for use cordarone ® (cordarone ®). Medicinal reference book geotar Preparation cordaron indications for use contraindications

Kordaron is used in the following cases to relieve an attack:

• paroxysmal tachycardia;
• paroxysmal ventricular tachycardia;
• paroxysmal supraventricular tachycardia with frequent contraction of the ventricles (Wolf-Parkinson-White syndrome);
• paroxysmal atrial fibrillation and its stable form (fibrillation and atrial flutter).

With the help of Kordaron, relapse prevention is also carried out:

• life-threatening ventricular arrhythmias and ventricular fibrillation;
• paroxysmal supraventricular tachycardias, including documented seizures in organic heart disease;
• documented attacks of sustained paroxysmal supraventricular tachycardia without organic heart disease in case of ineffectiveness of previously used antiarrhythmic drugs or contraindications;
• documented recurrent attacks of sustained paroxysmal supraventricular tachycardia with WPW syndrome;
• atrial fibrillation and atrial flutter.

The injectable form is intended for use to achieve an antiarrhythmic effect and when oral administration is not possible. The drug is used only in stationary conditions. Reviews about the drug can be read at the end of the article.

How to use

Tablet form

Loading dose:

• In the hospital: the initial dose, which is divided into several doses, should be from 600-800 mg (maximum = 1200 mg) per day to a total dose of 10 g (usually 5-8 days).
• Outpatient: the initial dose, which is divided into several doses, should be about 600-800 mg per day up to a total dose of 10 g (usually 10-14 days).
• Maintenance dose: 3 mg per kilogram of body weight in 1 day. It can be in the range of 100-400 mg per day with a single dose. It is recommended to use the minimum effective dose, based on individual therapeutic results.

Cordarone has a long half-life, in connection with this it can be taken every 2nd day (200 mg is given every 2nd day, and it is recommended to use 100 mg daily). You can take breaks 2 times a week).

Injection. Infusion intravenous

Loading dose

For adults - 5 mg per 1 kg of body weight, administered in 250 ml of a 5% glucose solution for 20 minutes - 2 hours. You can also enter two or three times during the day. The rate of infusion is adjusted according to the results.

The therapeutic effect is manifested in the first minutes of administration, gradually decreasing. Maintenance infusion required.

maintenance dose

For adults: 10 mg - 20 mg per 1 kg per 1 day (average value - 600 mg - 800 mg per 1 day, maximum dose - 1200 mg per 1 day) in 250 ml of a 5% glucose solution for several days. From the very beginning of treatment by infusion, it is necessary to begin the transition to the oral drug.

intravenous injection

Dose for adults - 5 mg per 1 kg. Injected within a minimum of 3 minutes. Re-injection is performed 15 minutes after the 1st injection, not earlier. To continue treatment, intravenous infusion is used.

Do not mix Kordaron with other medicines in the same syringe.

Composition, release form

Tablets

• Amiodarone hydrochloride - 200 mg (active substance);
• Lactose monohydrate 200 mesh. - 71.0 mg;
• Corn starch - 66.0 mg;
• K90F Polyvidone - 6.0 mg;
• Anhydrous colloidal silicon dioxide - 2.4 mg;
• Mg stearate - 4.6 mg per 1 divided tablet weighing 350.0 mg;

Injection

• Amiodarone hydrochloride 150 mg (active substance);
• Benzyl alcohol - 60 mg;
• Polysorbate 80 - 300 mg;
• Water for injection 3.0 ml.

Beneficial features

Cordarone is a class 3 antiarrhythmic drug that has antiarrhythmic and antianginal effects:

• the drug is able to block a-/b-adrenergic receptors;
• slows down atrial, sinoatrial and nodal conduction without affecting intraventricular;
• increases the refractory period of the accessory ventricular and atrial pathways;
• does not have a negative inotropic effect;
• reduces the contractility of the heart muscle after intravenous administration;
• affects metabolic processes thyroid hormones;
• inhibits the transition of hormones T3 to T4 and blocks their capture by cardiocytes and hepatocytes, which weakens the stimulation of thyroid hormones on the myocardium.

In plasma, it can be determined for up to nine months after you stop taking it. The therapeutic effect can be observed 1 week after the start of oral administration.

At intravenous administration Cordarone activity reaches its maximum level 15 minutes after administration and disappears after 4 hours. In spite of short term removal of the drug from the body, complete tissue saturation is achieved. In the absence of repetition of injections, the drug is excreted gradually. And upon renewal, a tissue reserve is formed.

Side effects

Organs of vision:

• deposition of lipofuscin in the epithelium of the cornea;
• rarely there are complaints of "fog" before the eyes in very bright light.

Dermatological reactions:

• otosensitization, manifested in the form of erythema in uncovered areas of the skin;
• rarely, slight pigmentation may appear on uncovered areas of the skin.

endocrine status:

• rarely, with long-term administration, the development of hypothyroidism is possible, very rarely, hyperthyroidism.

The cardiovascular system:

• at high doses of Kordaron, bradycardia may appear, AV conduction slows down, arterial hypotension.

Nervous system:

• possible rare cases development of peripheral neuropathy and tremor.

Gastrointestinal tract and liver:

• nausea;
• heaviness in the epigastrium;
• violations of the liver.

Respiratory system:

• there were cases of pneumonitis and alveolitis.

When used parenterally, a feeling of heat, sweating, bronchospasm is possible; in patients with severe heart failure, apnea is possible, intracranial pressure may increase, and a local reaction is phlebitis.

Contraindications

Tablets

• hypersensitivity to amiodarone and iodine;
• weak syndrome sinus node(sinus bradycardia, sinoatrial blockade), exception - cases of correction of an artificial pacemaker;
• violation of atrioventricular and intraventricular conduction;
• combination with drugs that can cause ventricular polymorphic tachycardia of the "pirouette" type;
• violation of the thyroid gland (hypothyroidism or hyperthyroidism);
• heart failure, hypokalemia;
• pregnancy, period breastfeeding;
• age less than 18 years (safety not established);
• simultaneous reception of MAO inhibitors;
• interstitial lung disease.

Injection

• allergy to amiodrone and iodine;
• sinus bradycardia, sinoatrial heart block;
• weak sinus node syndrome (exception - cases of correction by a pacemaker);
• serious violations conduction without the use of an artificial pacemaker,
• v complex treatment with drugs that cause ventricular paroxysmal tachycardia;
• violation of the thyroid gland;
• pregnancy, except in serious cases;
• lactation;
• childhood up to 3 years.

Interaction with other drugs

You can prescribe the drug together with cardiotonic drugs (for example, foxglove), but there is a risk of developing bradycardia.

Kordaron is prescribed together with diuretics and anticoagulants.

If Kordaron is taken for a long period before surgery, the drug will not have any adverse effect on resuscitation and anesthesia.

There are no known cases of Cordarone interaction with droperidol, chlorproxen, fenoperidone, dextromoramide, pentobarbital and pancuronium bromide.

It is not recommended to take Verampil and MAO inhibitors together with Kordaron. And also Kordaron should not be used together with beta-blockers (with the exception of some severe cases with hemodynamic features).

Terms and conditions of storage

Kordaron solution should be stored at room temperature not exceeding 25°C. Store in the original cardboard box, in a dry place, away from children.

Tablets should be stored below 28-30°C.

The drug Cordaron is released only on prescription. In the form of a solution for intravenous administration, it is intended for use exclusively in a hospital setting.

Price

The average price for Kordaron 200 mg tablets 30 pcs. in Ukraine and Russia is 128 UAH. and 300 rubles. respectively.

The average price of a Kordaron solution is 135 UAH and 320 rubles.

Analogues

• Amyocardin;
• Aritmil;
• Vero-Amiodarone;
• Rotarymil;

Kordaron is a drug that experts refer to the group of antiarrhythmic drugs. In its composition, the active compound is amiodarone hydrochloride. The drug is available in the form of tablets and solution for intravenous injection. This remedy is prescribed in the treatment of cardiac arrhythmias, as well as to eliminate angina pectoris, tachycardia and attacks of these diseases. During therapy with Kordaron a strong coronary dilating and adrenaline blocking effect is provided.

Kordaron: composition and form of release

Remedy offered in the form of tablets and solution. One tablet contains 200 mg of amiodarone hydrochloride as the active substance. Additional substances are the following components:

• povidone;
• starch;
• silica;
• lactose monohydrate;
• magnesium stearate.

Cordarone in the form of a solution contains 1 ml of 50 mg active substance. Additional components are:

• polysorbate;
• benzyl alcohol.

Reviews about the drug contain information about the main indications for the use of this medication. You can find out about them when reading instructions to Kordaron 200. The main indications for the appointment are the following cases:

Also, the drug Kordaron 200 is also prescribed as a prevention of relapses:

• atrial fibrillation and atrial flutter;
• ventricular arrhythmia and ventricular fibrillation. These conditions can pose a danger to the life of a sick person.

Application and dosage

Familiarization with the instructions for this drug helps each patient learn how to properly take this remedy. It states, that the drug Kordaron 200 in the form of tablets is taken orally before meals. The medicine should be taken with a small amount of water. Note that the dosage of the drug is determined by the attending physician, who is guided by clinical indications, and also takes into account the patient's condition.

When choosing loading "saturating" dose various saturation schemes can be used.

When carrying out treatment in stationary conditions, the initial dose of Kordaron 200 is 600-800 mg per day. The maximum dose of the drug should not exceed 1200 mg. Treatment is carried out until a total dose of the drug in the amount of 10 g is reached. Treatment according to this scheme usually lasts for 5-8 days.

For outpatient therapy starting dose varies from 600 to 800 mg. Therapy is carried out until a total dose of 10 g is reached. The duration of treatment does not exceed 14 days.

maintenance dose depending on on the condition of the patient can vary from 100 to 400 mg per day. It is necessary to use the minimum effective dose, focusing on the individual therapeutic effect. It is necessary to adhere to such a recommendation for the reason that Cordaron has a very large T1 / 2. It should be taken every other day or take breaks in taking it 2 days a week.

Kordaron: contraindications

Reviews of former patients about the treatment this drug contains information about contraindications to the use of Kordaron 200. The main ones include the following:

Instructions for the drug Cordaron 200 reports the presence of side effects. The patient may encounter them while taking this medicine. To the number most common side effects that occur during treatment with Kordaron include the following conditions:

Price

Kordaron tablets are a fairly common drug, so going to any pharmacy, you can purchase this tool. Kordaron 200 is offered at a price of 300 rubles. It is not necessary to purchase the remedy in a regular pharmacy. If there is a desire to buy a medicine at a low price, then it can be ordered via the Internet.

Analogues

Often in the treatment of heart disease patients have to use analogues. The need to purchase and use them is due to the fact that some patients, when they come to the pharmacy for this medicine, do not find the necessary medicine on the windows. And sometimes there are contraindications does not allow treatment original medicine. The group of analogues of this drug, which are most often prescribed by doctors, usually includes the following drugs:

• Amyocordin;
• Aritmil;
• Rotarymil;
• Cardiodarone.

Reviews

Previously, I did not pay much attention to the pain that arose in my heart area. However, at a certain point I had to think about the health of this organ. Faced with heart disease for the first time, I did not know what medications I should take to eliminate the discomfort that had arisen. Therefore, I had to seek qualified medical help. But the drugs prescribed by specialists did not help me.

Having come to an appointment with a new specialist, after the examination, he prescribed Kordaron 200 for me. By that time, I had already had the sad experience of using ineffective drugs, so I started taking the new drug with one blaster, which contained 10 tablets. The doctor prescribed me this medicine at a dosage of two tablets during the day. He also instructed to take 3 tablets per day if the pulse rate exceeds 90 beats per minute.

This remedy was prescribed after a diagnosis of cardiac arrhythmias, palpitations and high shallow respiration. All these symptoms were accompanied by severe pain in the chest area. I took Kordaron 200 together with Panangin.

Within a couple of hours after taking it, I had relief. I didn’t even believe that the drug worked so quickly. I tried to sit quietly so that the pain that had left my chest would not come back. On the third day of treatment, I forgot about the discomfort and felt only lightness.

Of course, I understand that taking Kordaron 200 is part of the treatment and you cannot prescribe other drugs on your own. You should trust the doctor and take the remedies prescribed by him, as well as follow all the instructions that he gave. About the drug Kordaron I want to say that although it is effective tool, but you can’t drink these pills for a long time, otherwise it can lead to certain health problems.

Elena Sergeevna

A few years ago, my mother faced such a problem as a severe arrhythmia. At the doctor's appointment, he prescribed Kordaron for her. She has been taking these pills for a long time and they help her well with the appearance of unpleasant sensations in the heart area. Although Kordaron tablets look unattractive, they provide a strong effect. As needed, when my mother has heart pain, she takes this drug in small doses.

She began therapy with half a pill. When such a small dose did not help her, she drank her soulmate. In the reviews, many patients write that in order to eliminate unpleasant symptoms in the heart area, it is enough to take 0.5 tablets of Kordaron. However, sometimes my mother had such pain that she had to take the whole pill. She likes the strong action in this preparation, which eliminates pain in the region of the heart.

After taking during the first hours, the pulse is restored, while attacks of arrhythmia are stopped. When my mother's blood pressure rises, she takes a drug that lowers blood pressure. Although Kordaron 200 is an effective remedy for arrhythmias, it must be taken with extreme caution. If you exceed the dosage, you may experience unpleasant symptoms. And then you have to call ambulance.

Valentina Mikhailovna

I did not go to the doctors for a long time, because until a certain point I did not have any health problems. However, a few months ago I faced such a problem as arrhythmia. severe pain in the area of ​​the heart made me come to the cardiologist. The specialist ordered an examination and, based on its results, said that I had paroxysmal tachycardia.

For the treatment of this disease, he prescribed me the drug Etatsizin. In the process of taking the resulting seizures, this medicine did not relieve. I have used the most different ways: performed clicks on eyeballs, held her breath and even tried to breathe more slowly to cut her pulse. Often had to call an ambulance to the house. Specialists injected drugs intravenously, but they did not provide the desired effect.

I also took other antiarrhythmic drugs. However, they did not bring serious relief. And often there was no reason for the appearance of seizures. Sometimes the attacks of arrhythmia lasted for 6 hours. This wore me down a lot.

Having visited another specialist at the reception, after the examination, he said that I had a very low pressure of 100/70. This is how he explained the fact that the drugs that I was prescribed earlier did not stop the attacks of arrhythmia.

So that I could cope with my problem, he prescribed me Cordaron, which is produced by a French company. I didn't even expect relief. However, after taking one pill, I was surprised to find that the attack stopped. I felt completely different. I have found a remedy that helps relieve pain.

About Kordaron I want to say that this medicine has a strong effect. Of course, it is not without contraindications. One of them is that this remedy should not be taken in the presence of serious thyroid diseases. It is also not necessary to arbitrarily carry out treatment with Kordaron. First you need to see a doctor. Having received the appointment of this drug, you must take it, observing the dosage. In this case, you can cope with arrhythmia.

Conclusion

Arrhythmia, tachycardia are serious diseases that many people face in adulthood. If you feel discomfort in the region of the heart that occurs with enviable constancy, then in this case you should immediately consult a doctor. Cardiologists often, when diagnosing tachycardia and arrhythmias, prescribe a drug such as Kordaron to patients. This remedy, which is produced by a French company, is quite effective. Its intake in accordance with the dosage prescribed by the doctor allows you to stop arrhythmia attacks and eliminate the symptoms of tachycardia.

This medicine is used for both outpatient and inpatient treatment. Before starting therapy, contraindications should be clarified. This drug should not be used during pregnancy, as well as during lactation. In addition, Kordaron is not prescribed to patients under 18 years of age. Such information can be found in the instructions for use, as well as in reviews. There are quite a few of them on the Internet. Many people who have recovered from arrhythmia indicate in their reviews how they were able to defeat the disease. From the reviews about this drug, you can learn a lot of other information that is of value to the patient.

The responses contain information about the correct use of the drug, contraindications, side effects, as well as the cost of the drug and its analogues. In terms of price, this tool is inexpensive. Reviews confirm this. If the drug was not in the pharmacy, then you can purchase and carry out treatment with analogues. A list of drugs that can act as drug substitutes is present in many reviews.

Note that the analogue of Kordaron 200 can only be prescribed by the attending physician. He also determines the treatment regimen that will ensure high efficiency of therapy. To quickly get rid of the disease, when the first signs of a violation of the heart appear, you should consult a doctor for an accurate diagnosis and adequate treatment. By following all the recommendations of a cardiologist, you can quickly get rid of the disease and return to normal life.

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Tablets are round, divided, white or white with a creamy tint, engraved with a symbol in the form of a middle and the number "200" on one side; tablets can be easily separated along the break line under normal conditions of use.

1 tab.
amiodarone hydrochloride 200 mg

Excipients: lactose monohydrate, corn starch, polyvidone K90F, anhydrous colloidal silicon dioxide, magnesium stearate.

10 pieces. - blisters (3) - packs of cardboard.

PHARMACHOLOGIC EFFECT

Class III antiarrhythmic drug. It has antiarrhythmic and antianginal effects.

The antiarrhythmic effect is due to an increase in the 3rd phase of the action potential, mainly due to a decrease in the potassium current through the channels of the cell membranes of cardiomyocytes and a decrease in the automatism of the sinus node. The drug non-competitively blocks α- and β-adrenergic receptors. Slows down sinoatrial, atrial and nodal conduction without affecting intraventricular conduction. Kordaron increases the refractory period and reduces myocardial excitability. Slows down the conduction of excitation and lengthens the refractory period of additional atrioventricular pathways.

The antianginal effect of Cordarone is due to a decrease in myocardial oxygen consumption (due to a decrease in heart rate and a decrease in OPSS), non-competitive blockade of α- and β-adrenergic receptors, an increase in coronary blood flow by direct action on the smooth muscles of the arteries, maintenance of cardiac output by reducing pressure in the aorta and a decrease in peripheral resistance .

Kordaron does not have a significant negative inotropic effect, reduces myocardial contractility mainly after intravenous administration.

It affects the metabolism of thyroid hormones, inhibits the conversion of T3 to T4 (thyroxine-5-deiodinase blockade) and blocks the capture of these hormones by cardiocytes and hepatocytes, which leads to a weakening of the stimulating effect of thyroid hormones on the myocardium. It is determined in the blood plasma for 9 months after stopping its intake.

Therapeutic effects are observed after 1 week (from several days to 2 weeks) after the start of oral administration of the drug.

With the on / in the introduction of Kordaron, its activity reaches a maximum after 15 minutes and disappears approximately 4 hours after administration. Despite the fact that the amount of Cordarone administered in the blood rapidly decreases, tissue saturation with the drug is achieved. In the absence of repeated injections, the drug is gradually eliminated. When resuming its administration or when prescribing the drug for oral administration, its tissue reserve is formed.

PHARMACOKINETICS

Suction

After oral administration, amiodarone is absorbed slowly (absorption is 30-50%), the absorption rate is subject to significant fluctuations. Bioavailability after oral administration ranges from 30 to 80% in different patients (on average, about 50%). After a single dose of the drug inside, Cmax in blood plasma is reached after 3-7 hours.

Distribution

Amiodarone has a large Vd. Amiodarone accumulates most in adipose tissue, liver, lungs, spleen and cornea. After a few days, amiodarone is excreted from the body. Css is achieved within 1 to several months, depending on the individual characteristics of the patient. Plasma protein binding - 95% (62% - with albumin, 33.5% - with beta-lipoproteins).

Metabolism

Metabolized in the liver. The main metabolite, deethylamiodarone, is pharmacologically active and may enhance the antiarrhythmic effect of the main compound. Each dose of Kordaron (200 mg) contains 75 mg of iodine; 6 mg of these were determined to be released as free iodine. With prolonged treatment, its concentrations can reach 60-80% of the concentrations of amiodarone.

breeding

Elimination by ingestion proceeds in 2 phases: T1 / 2 in the α-phase - 4-21 hours, T1 / 2 in the β-phase - 25-110 days. After prolonged oral administration, the average T1 / 2 is 40 days (this is important when choosing a dose, because it takes at least 1 month to stabilize plasma concentrations, and complete elimination can last more than 4 months).

After discontinuation of the drug, its complete elimination from the body continues for several months. The presence of pharmacodynamic effects of Kordaron should be taken into account for 10 days and up to 1 month after its cancellation. Amiodarone is excreted in bile and feces. Renal excretion is negligible.

Pharmacokinetics in special clinical situations

Insignificant excretion of the drug in the urine allows you to prescribe the drug for renal failure in medium doses. Amiodarone and its metabolites are not subject to dialysis.

INDICATIONS

Relief of attacks of ventricular paroxysmal tachycardia;

Relief of attacks of supraventricular paroxysmal tachycardia with a high frequency of ventricular contractions (especially against the background of WPW syndrome);

Relief of paroxysmal and stable forms of atrial fibrillation (atrial fibrillation) and atrial flutter.

Prevention of relapses

Life-threatening ventricular arrhythmias and ventricular fibrillation (treatment should be started in a hospital with careful cardiac monitoring);

Supraventricular paroxysmal tachycardias, incl. 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 WPW syndrome;

Atrial fibrillation (atrial fibrillation) and atrial flutter.

Prevention of sudden arrhythmic death in patients at high risk after a recent myocardial infarction with more than 10 ventricular extrasystoles in 1 hour, clinical manifestations chronic heart failure and reduced left ventricular ejection fraction (Cordaron is especially recommended for patients with organic heart disease (including coronary heart disease), accompanied by left ventricular dysfunction.

Kordaron for intravenous administration is intended for use only in a hospital in cases where a rapid achievement of an antiarrhythmic effect is required or when oral administration of the drug is not possible.

DOSING MODE

For oral administration

When prescribing the drug in a loading dose, various schemes can be used. When used in a hospital, the initial dose, divided into several doses, ranges from 600-800 mg / day to a maximum of 1200 mg / day (usually within 5-8 days).

For outpatient administration, the initial dose, divided into several doses, ranges from 600 mg to 800 mg / day (usually within 10-14 days).

The maintenance dose is determined at the rate of 3 mg / kg of body weight per day and can range from 100 mg / day to 400 mg / day when taken 1 time / day. The lowest effective dose should be used. Because Amiodarone has a very long half-life and can be taken every second day (200 mg can be given every other day, while 100 mg is recommended daily) or taken intermittently (2 days a week).

For solution for intravenous administration

The loading dose of Kordaron is initially 5-7 mg/kg of body weight in 250 ml of a 5% dextrose (glucose) solution for 30-60 minutes. The therapeutic effect of Kordaron appears during the first minutes of administration and disappears gradually, which requires correction of the rate of its administration in accordance with the results of treatment.

For maintenance therapy, the drug is prescribed as a continuous or intermittent (2-3 times / day) intravenous infusion in a 5% dextrose (glucose) solution for several days at a dose of up to 1200 mg / day. After intravenous administration at a loading dose, instead of continuing intravenous infusion, it is possible to switch to taking Kordarone orally at a dose of 600-800 mg to 1200 mg / day. From the first day of intravenous administration of Kordaron, it is advisable to start a gradual transition to taking the drug orally.

When conducting intravenous injections, the drug at a dose of 5 mg / kg is administered for at least 3 minutes. Kordaron should not be taken in the same syringe with other drugs!

For intravenous infusion, concentrations below 600 mg/l should not be used. For the preparation of solutions for intravenous administration, use only 5% dextrose (glucose) solution.

SIDE EFFECT

Solution for intravenous administration

Systemic reactions: sensation of heat, increased sweating, decrease in blood pressure (usually moderate and transient); cases of severe arterial hypotension or collapse (were reported with overdose or too rapid administration), moderate bradycardia (in some cases, especially in elderly patients, severe bradycardia and, in exceptional cases, stop the sinus node, requiring discontinuation of therapy); rarely - proarrhythmic action. At the beginning of therapy, there is an increase in the activity of hepatic transaminases in the blood serum, which usually remains moderate (1.5-3 times higher than upper bound norms /VGN/) and, as a rule, normalizes when the dose is reduced or even spontaneously. With a significant increase in the level of transaminases, treatment should be discontinued. There are separate reports of cases of acute liver failure with high levels of hepatic transaminases in the blood serum and / or jaundice (some fatal). In isolated (extremely rare) cases, anaphylactic shock, benign intracranial hypertension (brain pseudotumor), bronchospasm and/or apnea have been reported in patients with severe respiratory failure, especially in patients with bronchial asthma. Several cases of acute respiratory distress were observed, mainly associated with interstitial pneumonitis.

Local reactions: phlebitis (may be avoided by using a central venous catheter).

For oral administration

From the side of the cardiovascular system: bradycardia (mostly moderate and dose-dependent); in some cases (with dysfunction of the sinus node, in the elderly) - severe bradycardia; in exceptional cases - sinus blockade; rarely - conduction disturbances (sinoatrial blockade, AV blockade of various degrees, intraventricular blockade); in some cases - the emergence of new arrhythmias or aggravation of existing ones, in some cases - with subsequent cardiac arrest (according to the available data, it is impossible to establish a connection with the use of the drug, with the severity of heart damage or with treatment failure). These effects are observed mainly in cases of joint use of Kordaron with drugs that prolong the period of repolarization of the ventricles of the heart (QTc interval) or in violation of the electrolyte balance.

On the part of the organ of vision: microdeposits of lipofuscin in the cornea of ​​the eye (almost always present) are usually limited to the pupil area, reversible after discontinuation of the drug, sometimes lead to visual impairment in the form of a colored halo in bright light or a feeling of fog; in some cases, neuropathy / optic neuritis (the relationship with the intake of amiodarone has not yet been clearly established).

Dermatological reactions: photosensitivity; erythema (during radiotherapy); in some cases - a rash (usually non-specific), exfoliative dermatitis (the relationship with the drug has not been formally established); with prolonged use in high doses - grayish or bluish pigmentation of the skin (slowly disappears after stopping treatment).

From the endocrine system: an increase in the level of T3 in the blood serum (T4 remains normal or slightly reduced) in such cases in the absence of clinical signs thyroid dysfunction drug discontinuation is not required); possible development of hypothyroidism (mild weight gain, reduced activity, more pronounced / compared with expected / bradycardia); hyperthyroidism (both during therapy and within a few months after discontinuation of the drug). Suspicion of hyperthyroidism may occur with the following mild clinical symptoms: weight loss, arrhythmias, angina pectoris, heart failure. The diagnosis is confirmed by a clear decrease in serum TSH. Amiodarone should be discontinued.

From the digestive system: nausea, vomiting, taste disturbances (usually occur at the beginning of therapy when used in loading doses and decrease with dose reduction); at the beginning of treatment - an isolated increase (1.5-3 times higher than ULN) in the activity of hepatic transaminases (decrease with a decrease in the dose of the drug or even spontaneously); in some cases - acute disorders liver function and / or jaundice (require discontinuation of the drug), fatty hepatosis, cirrhosis. clinical symptoms and laboratory changes may be minimal (possible hepatomegaly, increased activity of hepatic transaminases increased up to 1.5-5 times compared with VGN); therefore, regular monitoring of liver function is recommended during treatment.

From the respiratory system: in some cases - pneumonitis, fibrosis, pleurisy, bronchiolitis obliterans with pneumonia (sometimes fatal), bronchospasm in patients with severe respiratory diseases (especially with bronchial asthma), acute respiratory distress syndrome in adults.

From the side of the central nervous system and peripheral nervous system: rarely - sensorimotor peripheral neuropathies and / or myopathies (usually reversible after discontinuation of the drug), extrapyramidal tremor, cerebellar ataxia; in rare cases - benign intracranial hypertension, nightmares.

Allergic reactions: rarely - vasculitis, kidney damage with increased creatinine levels, thrombocytopenia; in some cases - hemolytic anemia, aplastic anemia.

Others: alopecia; in some cases - epididymitis, impotence (the connection with the use of the drug has not been established).

CONTRAINDICATIONS

For oral administration

SSSU (sinus bradycardia, sinoatrial blockade) except for cases of correction by an artificial pacemaker;

Violations of AV and intraventricular conduction (AV blockade II and III degree, blockade of the legs of the bundle of His) in the absence of an artificial pacemaker (pacemaker);

Thyroid dysfunction (hypothyroidism, hyperthyroidism);

hypokalemia;

Heart failure (in the stage of decompensation);

Simultaneous reception of MAO inhibitors;

Interstitial lung disease;

Pregnancy;

Lactation;

For solution for intravenous administration

SSSU (sinus bradycardia, sinoatrial blockade) with the exception of patients with an artificial pacemaker (danger of stopping the sinus node);

AV block II and III degree, violations of intraventricular conduction (blockade of two and three legs of the bundle of His); in these cases, intravenous amiodarone can be used in specialized departments under the cover of an artificial pacemaker (pacemaker);

Acute cardiovascular failure(shock, collapse);

Severe arterial hypotension;

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

Thyroid dysfunction (hypothyroidism, hyperthyroidism);

Pregnancy;

Lactation;

Age up to 18 years (efficacy and safety not established);

Hypersensitivity to iodine and/or amiodarone.

In / in the introduction is contraindicated in severe impairment of lung function (interstitial lung disease), cardiomyopathy or decompensated heart failure (possibly worsening of the patient's condition).

Use with caution in chronic heart failure, liver failure, bronchial asthma, in old age (due to the high risk of developing severe bradycardia).

PREGNANCY AND LACTATION

During pregnancy, Kordaron is prescribed only for health reasons, because. the drug has an effect on thyroid gland fetus.

Amiodarone is excreted in breast milk in significant quantities, so the drug is contraindicated for use during lactation.

SPECIAL INSTRUCTIONS

An ECG study is recommended before and during treatment. Due to the prolongation of the period of repolarization of the ventricles of the heart, pharmachologic effect Cordarone causes certain changes in the ECG: prolongation of the QT interval, QTc, the appearance of U waves is possible. An increase in the QTc interval is not more than 450 ms or not more than 25% of the original value. These changes are not a manifestation of the toxic effect of the drug, but require monitoring for dose adjustment and evaluation of the possible proarrhythmic effect of Kordaron.

It should be borne in mind that in elderly patients there is a more pronounced decrease in heart rate.

With the development of AV block II or III degree, sinoatrial or bifascicular blockade, treatment with Cordaron should be discontinued.

The appearance of shortness of breath or an unproductive cough may be associated with the toxic effect of Kordaron on the lungs. In patients with increasing dyspnoea during physical exertion, regardless of the deterioration of their general condition (increased fatigue, weight loss, fever), x-rays should be taken before starting therapy. chest. Respiratory disorders are mostly reversible with early withdrawal of amiodarone. Clinical symptoms usually disappear within 3-4 weeks, and then there is a slower recovery of the x-ray picture and lung function (several months). Therefore, consideration should be given to reevaluating amiodarone therapy and prescribing corticosteroids.

If there is blurred vision or a decrease in visual acuity while taking Kordaron, it is recommended to conduct a complete ophthalmological examination, including fundoscopy. Cases of optic neuropathy and / or optic neuritis require a decision on the advisability of using Kordaron.

Cordarone contains iodine (200 mg contains 75 mg of iodine), so it can affect the results of tests for the accumulation of radioactive iodine in the thyroid gland, but does not affect the reliability of determining T3, T4 and TSH. Amiodarone can cause thyroid dysfunction, especially in patients with a history of thyroid dysfunction (including family history). Therefore, before the start of treatment, during treatment and several months after the end of treatment, careful clinical and laboratory monitoring should be carried out. If thyroid dysfunction is suspected, serum TSH levels should be measured. When signs of hypothyroidism appear, normalization of thyroid function is usually observed within 1-3 months after stopping treatment. In life-threatening situations, treatment with amiodarone may be continued, with simultaneous additional administration of levothyroxine. TSH level blood serum serve as a guideline in the dosage of levothyroxine. If signs of hyperthyroidism appear, amiodarone should be discontinued. Normalization of thyroid function usually occurs within a few months after discontinuation of the drug. In this case, the clinical symptoms normalize earlier than the normalization of the level of hormones that reflect the function of the thyroid gland occurs. In severe cases, urgent medical intervention is required. Treatment in each individual case is selected individually and includes antithyroid drugs (which may not always be effective), corticosteroids, beta-blockers.

Kordaron for intravenous administration is used only in a specialized department of a hospital under constant monitoring of ECG, blood pressure. In this case, Kordaron should be administered as infusions, and not as injections, due to the risk of hemodynamic disturbances (arterial hypotension, acute cardiovascular insufficiency).

In / in injections of Kordaron should be carried out only in emergency situations, when there are no other therapeutic options, and only in cardio intensive care units with continuous ECG monitoring.

When Cordarone is administered as an injection, a dose of about 5 mg/kg should be administered over at least 3 minutes. The injection should not be repeated earlier than 15 minutes after the first injection, even if the latter consisted of only one ampoule (irreversible collapse is possible).

Special care is required when infusing the drug in case of arterial hypotension, severe respiratory failure, decompensated cardiomyopathy or severe heart failure.

Patients should avoid prolonged sun exposure and UV exposure (or use sunscreen).

Influence on the ability to drive vehicles and control mechanisms

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

OVERDOSE

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

Treatment: carry out symptomatic therapy(gastric lavage, the appointment of cholestyramine, with bradycardia - beta-adrenergic stimulators or the installation of a pacemaker, with tachycardia of the "pirouette" type - intravenous administration of magnesium salts, slowing down pacing). Amiodarone and its metabolites are not removed by dialysis.

There is no information on overdose with the on / in the introduction of Kordaron.

DRUG INTERACTIONS

While taking Kordaron with antiarrhythmic drugs (including bepridil, class I A drugs, sotalol), as well as with vincamine, sultopride, erythromycin for intravenous administration, pentamidine for parenteral administration, the risk of developing polymorphic paroxysmal ventricular tachycardia of the "pirouette" type increases. Therefore, these combinations are contraindicated.

Combination therapy with beta-blockers, some calcium channel blockers (verapamil, diltiazem) is not recommended. disturbances of automatism (manifested by bradycardia) and conduction may develop.

It is not recommended to use Kordaron simultaneously with laxatives (stimulating intestinal motility), which can cause hypokalemia, tk. the risk of developing ventricular tachycardia of the "pirouette" type increases.

With caution, Kordaron should be used simultaneously with drugs that cause hypokalemia (diuretics, systemic corticosteroids and mineralocorticoids, tetracosactide, amphotericin B / for intravenous administration /), because development of ventricular tachycardia of the "pirouette" type is possible.

With the simultaneous use of Kordaron with oral anticoagulants, the risk of bleeding increases (therefore, it is necessary to control the level of prothrombin and adjust the dose of anticoagulants).

With the simultaneous use of Kordaron with cardiac glycosides, automatism disturbances (manifested by severe bradycardia) and atrioventricular conduction disturbances may be observed. In addition, it is possible to increase the concentration of digoxin in the blood plasma due to a decrease in its clearance (therefore, it is necessary to control the concentration of digoxin in the blood plasma, conduct an ECG and laboratory monitoring, and, if necessary, change the dosing regimen of cardiac glycosides).

With the simultaneous use of Kordaron with phenytoin, cyclosporine, flecainide, an increase in the concentration of the latter in the blood plasma is possible (therefore, the concentration of phenytoin, cyclosporine, flecainide in the blood plasma should be monitored and, if necessary, their dose should be adjusted).

Cases of bradycardia (resistant to atropine), arterial hypotension, conduction disturbances, and a decrease in cardiac output in patients taking Kordaron and undergoing general anesthesia are described.

When using oxygen therapy in the postoperative period in patients treated with Kordaron, rare cases of the development of severe respiratory complications, sometimes ending in death (acute respiratory distress syndrome in adults), are described.

When used together with simvastatin, it is possible to increase the risk of side effects (primarily rhabdomyolysis) due to a violation of the metabolism of simvastatin (if necessary, the use of such a combination, the dose of simvastatin should not exceed 20 mg / day, if the therapeutic effect is not achieved at this dose, you should switch to another lipid-lowering drug).

TERMS AND CONDITIONS OF DISCOUNT FROM PHARMACIES
The drug is dispensed by prescription. The drug in the form of a solution for intravenous administration is intended for use only in a hospital setting.

TERMS AND CONDITIONS OF STORAGE

The drug in the form of tablets should be stored at room temperature (not higher than 30°C). The shelf life of the tablets is 3 years. The drug in the form of a solution for intravenous administration should be stored in a dry place at a temperature not exceeding 25 ° C. The shelf life of the solution for intravenous administration is 2 years.

Cordarone is a drug of synthetic origin. This tool is sold in tablets of 0.2 g each in packs of 60 pieces and in 3 ml ampoules in a 5% solution. Cordarone has a versatile effect on the cardiovascular system, including reducing the load on the heart, improving blood supply to the heart muscle, making heart contractions more rare and lowering blood pressure.

Cordarone is widely used in cardiology. Sometimes Kordaron is used by patients who have WPW syndrome. It can also be prescribed for angina pectoris, especially for patients whose attacks occur with excessive physical or mental stress, as well as with various cardiac arrhythmias, which are accompanied by extrasystole - increased heart rate.

Kordaron instructions for use: this drug is prescribed for oral administration with or after meals. The recommended way of Kordaron's application: 5 days, and then a break for 2 days. The dose of the drug and the duration of use are set only by a doctor. Kordaron is also sometimes prescribed intravenously to stop arrhythmia attacks. The price of Cordanone, as well as the price of Propafenone (a drug also used in WPW syndrome) is not very high.

As a rule, Kordaron is well tolerated by all people, but sometimes nausea and stool disorders may occur after taking the drug. When taking large doses at the beginning of treatment, bradycardia may occur, that is, the pulse drops below 60 beats per minute. Prolonged use of Kordaron may be accompanied by the appearance of increased skin sensitivity to sunlight. If the drug is prescribed for a period of more than 20 months, then the skin of the face and hands may become covered with gray pigmentation; pigment may be deposited in the cornea of ​​the eyes, there may be slight interference in vision, itching in the eyes. These phenomena disappear a year after the end of the drug.

It is necessary to be careful in patients with impaired thyroid function taking Kordaron. In general, long-term use of Kordaron may be accompanied by some side effects, so you should always consult your doctor.

If the patient also takes cardiac glycosides along with Kordaron, intoxication may occur. It is also required to be careful when combining the intake of Kordaron and anaprilin, novocainamide, verapamil. Together, these drugs should not be taken without consulting a doctor. Cordarone is contraindicated in people with a slow heart rate, bronchial asthma, thyroid insufficiency, low blood pressure, pregnancy, over 70 years of age.

www.doverie.org

Kordaron: instructions for use of the drug

Tablets Prevention of recurrence: life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be started in a hospital with careful cardiac monitoring); supraventricular paroxysmal tachycardia: 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 high-risk patients: after a recent myocardial infarction, with more than 10 ventricular extrasystoles per hour, clinical manifestations of chronic heart failure and a reduced left ventricular ejection fraction (less than 40%). treatment of arrhythmias in patients with ischemic heart disease and / or impaired left ventricular function. Injection form of Kordaron® relief of attacks of ventricular paroxysmal tachycardia; supraventricular paroxysmal tachycardia with a high frequency of ventricular contractions, especially against the background of Wolff-Parkinson-White syndrome; relief of paroxysmal and stable forms of atrial fibrillation (atrial fibrillation) and atrial flutter;

cardioresuscitation in cardiac arrest caused by ventricular fibrillation resistant to cardioversion.

Solution for intravenous administration 50 mg/ml; ampoule 3 ml, contour plastic packaging (pallets) 6, cardboard pack 1; Composition Tablets divisible 1 tab. amiodarone hydrochloride 200 mg excipients: lactose monohydrate; corn starch; magnesium stearate; povidone K90F; silicon dioxide colloidal anhydrous in a blister 10 pcs.; in a box of 3 blisters. Solution for intravenous administration 3 ml amiodarone hydrochloride 150 mg excipients (per ampoule): benzyl alcohol - 60 mg; polysorbate 80 - 300 mg; water for injection - up to 3 ml

in ampoules of 3 ml; in a box of 6 pcs.

Amiodarone belongs to the III class of antiarrhythmic drugs (a class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action, because. 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 antiarrhythmic action, it has antianginal, coronary dilating, alpha and beta adrenoblocking effects. Antiarrhythmic properties: - 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 class III according to the Vaughan-Williams classification); - a decrease in the automatism of the sinus node, leading to a decrease in the heart rate; - non-competitive blockade of alpha and beta adrenergic receptors; - slowing of sinoatrial, atrial and AV conduction, more pronounced with tachycardia; - no changes in ventricular conduction; - an increase in refractory periods and a decrease in the excitability of the myocardium of the atria and ventricles, as well as an increase in the refractory period of the AV node; - slowing conduction and an increase in the duration of the refractory period in additional bundles of atrioventricular conduction. Other effects: - no negative inotropic effect when taken orally and parenterally; - reduction of oxygen consumption by the myocardium due to a moderate decrease in peripheral resistance and heart rate, as well as myocardial contractility due to beta-blocking action; - an increase in coronary blood flow due to a direct effect on smooth muscles coronary arteries; - maintenance of cardiac output by reducing pressure in the aorta and reducing peripheral resistance; - influence on the metabolism of thyroid hormones: inhibition of the conversion of T3 to T4 (thyroxine-5-deiodinase blockade) and blocking the uptake of these hormones by cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium. - restoration of cardiac activity in cardiac arrest caused by ventricular fibrillation resistant to cardioversion.

Therapeutic effects are observed on average one week after the start of the drug (from several days to two weeks). After stopping its intake, amiodarone is determined in the blood plasma for 9 months. The possibility of maintaining the pharmacodynamic action of amiodarone for 10-30 days after its withdrawal should be taken into account.

Bioavailability after oral administration in different patients ranges from 30 to 80% (the average value is about 50%). After a single dose of amiodarone, Cmax in plasma is reached after 3-7 hours. However, the therapeutic effect usually develops a week after the start of the drug (from several days to 2 weeks). Amiodarone is a slow-release, high-affinity drug. Plasma protein binding is 95% (62% with albumin, 33.5% with beta-lipoproteins). Amiodarone has a large volume of distribution. During the first days of treatment, the drug accumulates in almost all tissues, especially in adipose tissue and in addition to it in the liver, lungs, spleen and cornea. Amiodarone is metabolized in the liver. Its main metabolite, deethylamiodarone, is pharmacologically active and may enhance the antiarrhythmic effect of the main compound. Amiodarone is an inhibitor of hepatic isoenzymes of microsomal oxidation: CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP3A7. Removal of amiodarone begins after a few days, and the achievement of equilibrium between the intake and excretion of the drug (achievement of an equilibrium state) occurs after one to several months, depending on the individual characteristics of the patient. The main route of excretion of amiodarone is the intestine. Amiodarone and its metabolites are not excreted by hemodialysis. Amiodarone has a long T1 / 2 with great individual variability (therefore, when selecting a dose, for example, increasing or decreasing it, it should be remembered that at least 1 month is needed to stabilize the new plasma concentration of amiodarone). Elimination by ingestion proceeds in 2 phases: initial T1 / 2 (first phase) - 4-21 hours, T1 / 2 in the 2nd phase - 25-110 days (20-100 days). After a long oral intake average T1 / 2 - 40 days. After discontinuation of the drug, the complete elimination of amiodarone from the body can last for several months. Each dose of amiodarone (200 mg) contains 75 mg of iodine. Part of the iodine is released from the drug and is found in the urine in the form of iodide (6 mg / day at a daily dose of amiodarone 200 mg). Most of the iodine remaining in the drug is excreted in the feces after passing through the liver, however, with prolonged use of amiodarone, iodine concentrations can reach 60-80% of the concentrations of amiodarone. The peculiarities of the pharmacokinetics of the drug explain the use of "loading" doses, which is aimed at quickly achieving the required level of tissue saturation, at which its therapeutic effect is manifested. Pharmacokinetics in renal failure: due to the insignificance of the excretion of the drug by the kidneys in patients with kidney failure no dose adjustment of amiodarone is required. With the on / in the introduction of Kordaron®, its activity reaches a maximum after 15 minutes and disappears approximately 4 hours after administration. After the introduction of amiodarone, its concentration in the blood decreases rapidly due to the flow of the drug into the tissues. In the absence of repeated injections, the drug is gradually eliminated. With the resumption of its intravenous administration or with the appointment of the drug inside, amiodarone accumulates in the tissues. Amiodarone has a large volume of distribution and can accumulate in almost all tissues, especially in adipose tissue and in addition to it in the liver, lungs, spleen and cornea Amiodarone and its metabolites do not undergo dialysis.

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

Pregnancy Currently available clinical information is not sufficient to determine whether or not fetal malformations may occur when using amiodarone during 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 in case of its earlier use. An excess of iodine when using the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in a newborn or even to the formation of a clinically significant goiter in him. Due to the effect of the drug on the thyroid gland of the fetus, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit outweighs the risk (with life-threatening ventricular arrhythmias). lactation period

Amiodarone is secreted into breast milk in significant quantities, so it is contraindicated during lactation (therefore, during this period, the drug should be discontinued or breastfeeding stopped).

Common for both dosage forms hypersensitivity to iodine, amiodarone or excipients of the drug; syndrome of weakness of the sinus node (sinus bradycardia, sinoatrial blockade), except in cases of correction by an artificial pacemaker (danger of "stopping" the sinus node). AV blockade II-III degree, two- and three-beam blockade in the absence of an artificial pacemaker (pacemaker); hypokalemia, hypomagnesemia; combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including polymorphic ventricular tachycardia of the "pirouette" type (torsade de pointes) (see "Interaction"): - antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide procainamide); class III antiarrhythmic drugs (dofetilide, ibutilide, bretylium tosylate); sotalol; - other (non-antiarrhythmic) drugs such as bepridil; 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; antimalarials (quinine, chloroquine, mefloquine, halofantrine); pentamidine when administered parenterally; diphemanil methyl sulfate; mizolastin; astemizole, terfenadine; fluoroquinolones. congenital or acquired prolongation of the QT interval. thyroid dysfunction (hypothyroidism, hyperthyroidism). pregnancy (see "Use during pregnancy and lactation"); lactation period (see "Use during pregnancy and lactation"); age up to 18 years (efficacy and safety have not been established). For tablets additionally: interstitial lung disease. For the injection form, additionally: violations of intraventricular conduction (two- and three-beam blockades) in the absence of a permanent artificial pacemaker (pacemaker) - in these cases, intravenous amiodarone can be used in specialized departments under the cover of an artificial pacemaker (pacemaker); severe arterial hypotension, collapse, cardiogenic shock. All of the above contraindications do not apply to the use of Kordaron® during cardioresuscitation in cardiac arrest caused by ventricular fibrillation resistant to cardioversion.

Use with caution in arterial hypotension, decompensated or severe chronic (III-IV FC according to NYHA classification) heart failure, liver failure, bronchial asthma, severe respiratory failure, in elderly patients (high risk of developing severe bradycardia), with AV blockade of the first degree .

The frequency of side effects was defined as follows: very often - ≥10%), often - ≥1%,

med36.com

Kordaron - Reviews about Kordaron

Description and instructions of the drug Kordaron

Kordaron is a drug that is prescribed for arrhythmias and angina pectoris. Its active ingredient is amiodarone, which is also available as an independent drug. This active substance has antiarrhythmic activity, reducing the excitability of the heart muscle. A similar effect is achieved by blocking the potassium channels of the membranes of the heart muscle cells. Calcium and sodium ion channels are less affected by this drug. The antianginal efficacy of Kordaron is explained by its ability to expand the coronary vessels and reduce their resistance, slow down the heart rate and reduce myocardial oxygen demand. The effect of the drug on the patient's body develops gradually. The effect of Kordaron "accumulates" and can manifest itself one and a half to two weeks after the end of the course. This drug is used for arrhythmias of various forms and origins, Wolf-Parkinson-White syndrome, angina pectoris and its prevention, during the recovery period after myocardial infarction.

Cordaron is produced both in the form of tablets and in the form of a solution for injection. The instruction of the drug describes in sufficient detail the scheme of its use, because there are nuances associated with the need to "accumulate" the active components of the drug in the body, and then maintain the achieved effect. For example, when using Kordaron tablets, you should start with higher doses that are taken with food (or after eating), and when a noticeable result is achieved, the treatment enters the maintenance phase. During this period, which can last for years (up to two years), the patient uses the minimum maintenance dose of the drug. Depending on the patient's well-being and how he tolerates Kordaron, a regimen with interruptions in taking the medication may be prescribed. Intravenous infusions of drugs give a quick therapeutic effect and are used in case of emergency therapy, for example, with ventricular fibrillation. But still, it is preferable to use the drug in tablets - which is started as soon as the patient's health allows.

The use of Kordaron is not shown in case of intolerance to its active substance, as well as iodine and other auxiliary components of the drug. In addition, this medicine is not prescribed for slow heart rate, weakness of the sinus node or blockade of cardiac conduction, with severe forms of hypotension and heart failure, with thyroid diseases. Pregnant and breastfeeding women should not receive Cordarone treatment.

Side effects and overdose of Kordaron

The drug has a systemic effect on the body. In addition to the cardiovascular system, which is primarily and directly exposed to Kordaron, reactions are also possible from the side of the organs of vision - in the form of vague contours or the appearance of colored halos around objects; from the side of the thyroid gland - hypothyroidism and so on; from the nervous system - myopathy, neuropathy, sleep disturbances, and so on.

With a single use of a highly overestimated dose of Kordaron, the expected effects on the part of cardiac activity and the state of blood vessels develop: the heart rhythm slows down, conduction blockade may occur, vascular resistance drops and hypotension develops. All of the above can lead to cardiac arrest. If there is hope to remove excess drug from the body, then gastric lavage can be performed and adsorbents given to the patient (activated charcoal, for example). To activate the work of the heart, atropine is administered, pacing is used.

Reviews about Cordarone

Patients who are prescribed this drug confirm that they have to regularly monitor the condition of the thyroid gland. At the same time, some reviews of Cordarone tell us that the state of the endocrine system has noticeably worsened, hypothyroidism has begun. There are reviews that tell about other undesirable symptoms that accompany taking Cordaron, for example, constipation. The presence of side effects often forces patients to seek a replacement for this drug.

But still, the main thing when using Kordaron is its ability or inability to normalize the heart rhythm. If the drug copes with this task, then during certain periods of therapy it can and should be used.

zhivizdorovim.ru

Kordaron

Cordarone is an antiarrhythmic drug used to treat diseases of the cardiovascular system.

Release form and composition

The following dosage forms of Kordaron are produced:

• Tablets: round from white with a creamy tint to white. On one side - a fault line, on both sides - a bevel from the edges to the fault line and engraving "200" under it, a chamfer and a heart-shaped symbol above the fault line (in blisters of 10 pcs; 3 blisters in a carton box);
• Solution for intravenous administration: light yellow transparent (in 3 ml colorless glass ampoules with two marking rings and a break point in the upper part; in plastic blister packs of 6 ampoules; in a carton pack 1 pack).

The composition of 1 tablet includes:

• Active substance: amiodarone hydrochloride - 0.2 g;
• Auxiliary components: magnesium stearate, anhydrous colloidal silicon dioxide, lactose monohydrate, povidone K90F, corn starch.

1 ampoule contains:

• Active ingredient: amiodarone hydrochloride - 0.15 g;
• Auxiliary components: polysorbate 80 - 0.3 g, water for injection - up to 3 ml, benzyl alcohol - 0.06 g.

Indications for use

For solution:

• Cardiac resuscitation in cardiac arrest (due to defibrillation-resistant ventricular fibrillation);
• Relief of attacks: supraventricular paroxysmal tachycardia with a high frequency of ventricular contractions (especially in Wolff-Parkinson-White syndrome); ventricular paroxysmal tachycardia; relief of a stable and paroxysmal form of atrial fibrillation and atrial flutter;

For tablets (relapse prevention):

• Fibrillation and atrial flutter;
• Life-threatening ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia;
• Supraventricular paroxysmal tachycardias: Documented attacks of recurrent sustained paroxysmal supraventricular tachycardia in patients with organic heart disease, Wolff-Parkinson-White syndrome, and without organic heart disease, when therapy with antiarrhythmic drugs of other classes has not been effective, or there are contraindications to their use.

Also, tablets are taken to prevent sudden arrhythmic death in patients at high risk: patients after a recent myocardial infarction, in whom the number of ventricular extrasystoles in 1 hour exceeds 10, the left ventricular ejection fraction is reduced (less than 40%) and there are clinical manifestations of chronic heart failure.

It is allowed to use the drug for the treatment of rhythm disturbances in patients with impaired left ventricular function and / or ischemic disease hearts.

Contraindications

Both dosage forms of Kordaron are contraindicated for use in the following diseases / conditions:

• Thyroid dysfunction (hyperthyroidism, hypothyroidism);
• Prolongation of the QT interval (congenital or acquired);
• Sinus node weakness syndrome (sinoatrial blockade, sinus bradycardia) in the absence of a permanent artificial pacemaker (pacemaker), due to the danger of stopping the sinus node;
• Age up to 18 years;
• Hypomagnesemia, hypokalemia;
• Pregnancy and the period of breastfeeding (lactation);
• Atrioventricular (AV) block II-III degree in the absence of a pacemaker;
• Simultaneous use with drugs that can cause the development of paroxysmal tachycardia (including ventricular torsades de pointes) and prolong the QT interval: class I A antiarrhythmic drugs (disopyramide, hydroquinidine, procainamide, quinidine) and class III (bretylium tosylate, ibutilide, dofetilide); other (non-antiarrhythmic) drugs (bepridil); sotalol; vincamine; pentamidine when administered parenterally; some neuroleptics phenothiazines (trifluoperazine, cyamemazine, fluphenazine, chlorpromazine, thioridazine, levomepromazine), butyrophenones (haloperidol, droperidol), benzamides (sulpiride, sultopride, amisulpride, veralipride, tiapride), pimozide, sertindole; cisapride; antibiotic drugs of the macrolide group (in particular, erythromycin when administered intravenously, spiramycin); tricyclic antidepressants; antimalarial drugs (chloroquine, quinine, halofantrine, mefloquine); fluoroquinolones; azoles; mizolastin; diphemanil methyl sulfate; terfenadine, astemizole;
• Hypersensitivity to amiodarone, iodine or auxiliary components of the drug.

For the use of the solution, contraindications are:

• Severe arterial hypotension, collapse, cardiogenic shock;
• Intraventricular conduction disturbances in the absence of a pacemaker. In such cases intravenous use the drug is permissible only in specialized departments under the guise of a temporary pacemaker;
• Intravenous stream administration: arterial hypotension, severe respiratory failure, cardiomyopathy or heart failure.

All of the above contraindications do not apply to the use of Kordaron in cases of cardiac resuscitation caused by cardiac arrest and ventricular fibrillation resistant to defibrillation.

Tablets should not be used if diagnosed:

• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;
• Interstitial lung disease.

Use with caution:

• Solution and tablets for: liver failure, severe respiratory failure, bronchial asthma, decompensated or severe heart failure, AV blockade I degree, in elderly patients;
• Solution: in case of arterial hypotension.

Method of application and dosage

Tablets are taken orally before meals, drinking plenty of water.

To calculate the loading (saturating) dose, various saturation schemes can be applied.

In a hospital setting: the initial dose is 0.6-0.8 g (up to a maximum of 1.2 g) per day, divided into several doses, until a total of 10 g is reached (usually within 5-8 days).

On an outpatient basis: the initial dose, divided into several doses, is 0.6-0.8 g per day until a total of 10 g is reached (usually within 10-14 days).

The daily maintenance dose in different patients may vary from 0.1 to 0.4 g. The minimum effective dose should be used in accordance with the individual therapeutic effect.

Since the half-life of the drug is long, it is allowed to use it every other day or with interruptions in taking it 2 times in 7 days.

The average and maximum doses of Kordaron are:

• Average therapeutic one-time - 0.2 g;
• The average therapeutic daily allowance is 0.4 g;
• Maximum single - 0.4 g;
• Maximum daily - 1.2 g.

The solution is used in cases where the use of the drug inside is impossible or it is necessary to quickly achieve an antiarrhythmic effect. It must be used only in a hospital in the intensive care unit under constant monitoring of the electrocardiogram (ECG) and blood pressure(HELL).

It should be borne in mind that when administered intravenously:

• The drug must not be mixed with other drugs;
• In the line of the infusion system used for the introduction of Kordaron, other drugs should not be administered;
• Medicine used only in diluted form;
• To dilute Kordaron, it is necessary to use only 5% dextrose (glucose) solution;
• Due to the existing features of the Cordaron solution, the use of concentrations of the infusion solution is less than those obtained by diluting 2 ampoules in 500 ml of 5% dextrose (glucose) is not recommended;
• To avoid reactions at the injection site, the solution must be administered through a central venous catheter. An exception is cases of cardioresuscitation in defibrillation-resistant ventricular fibrillation, when, due to the lack of central venous access, peripheral veins can be used to administer the solution.

Dosing regimen for severe cardiac arrhythmias, when the drug is not taken orally (the exception is cardioresuscitation during cardiac arrest caused by defibrillation-resistant ventricular fibrillation).

Intravenous drip solution through a central venous catheter:

• Loading dose - 0.005 g per 1 kg of body weight, diluted in 250 ml of 5% dextrose (glucose) solution. The introduction, if possible, is carried out using an electronic pump for 20-120 minutes (may be repeated 2-3 times within 24 hours). Depending on the clinical effect, the rate of administration of the solution is adjusted. During the first minutes after the administration of the drug, a therapeutic effect appears, gradually decreasing after the infusion is stopped. In this regard, if it is necessary to continue therapy with an injectable form of the drug, it is recommended to switch to a permanent intravenous drip;
• Maintenance daily doses - 0.01-0.02 g / kg (usually 0.6-0.8 g, but can be increased to 1.2 g) in 250 ml of 5% dextrose (glucose) solution for several days. From the first day of infusion, it is necessary to start a gradual transition to taking the drug orally (3 tablets of 0.2 g / day, with a possible increase to 4-5 pieces of 0.2 g / day).

Intravenous jet administration:

• Dose - 0.005 g per 1 kg of body weight, should be carried out for at least 3 minutes. An exception is cases of cardioresuscitation in defibrillation-resistant ventricular fibrillation. Re-introduction is carried out no earlier than 15 minutes after the first injection, even if the contents of only one ampoule were used for the first injection (due to the possibility of irreversible collapse);
• If it is necessary to continue the administration of amiodarone, it should be administered as an infusion.

Because of the hemodynamic risk, this route of administration is generally not recommended. Preferably infusion administration of Kordaron (if possible).

Intravenous jet administration 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 first dose of the drug in cases of cardiac resuscitation during cardiac arrest caused by defibrillation-resistant ventricular fibrillation is 0.3 g or 0.005 g / kg after dilution in 20 ml of a 5% dextrose (glucose) solution. It is administered intravenously-stream.

In cases where fibrillation is not stopped, an additional intravenous jet injection of 0.15 g (or 0.0025 g / kg) is allowed.

Side effects

The use of Kordaron can cause side effects from some body systems.

Tablets:

• Digestive system: very often - nausea, dysgeusia, vomiting (usually observed when taking a loading dose and pass after its reduction);
• Cardiovascular system: often - bradycardia (usually moderate), its severity depends on the dose of the drug; infrequently - a violation of the conduction of the heart, arrhythmogenic effect; very rarely - vasculitis; severe bradycardia or, in exceptional cases, stop of the sinus node; with an unknown frequency - ventricular tachycardia of the pirouette type, progression of chronic heart failure (with prolonged use);
• Respiratory system: often - pulmonary toxicity, sometimes fatal; very rarely - bronchospasm, acute respiratory distress syndrome (sometimes fatal); with an unknown frequency - pulmonary bleeding;
• Liver and biliary tract: very often - an isolated increase in serum transaminase activity, usually moderate (decreases spontaneously or with a decrease in dose); often - acute liver damage with jaundice and / or increased activity of transaminases, including the development of liver failure (sometimes fatal); very rarely - chronic liver disease, sometimes fatal. A moderate increase in the activity of transaminases in the blood observed after therapy, which lasted more than six months, is the basis for suspecting chronic liver damage;
• Endocrine system: often - hypothyroidism; hyperthyroidism (sometimes fatal), the appearance of which is possible not only during therapy, but also after its completion; mental disorders in elderly patients or even thyrotoxicosis phenomena; very rarely - a syndrome of impaired secretion of antidiuretic hormone;
• Organ of vision: very often - microdeposits in the epithelium of the cornea, usually limited to the pupil area, consisting of complex lipids, including lipofuscin. Sometimes they cause visual disturbances in the form of the appearance of a colored halo or fuzzy contours in bright light; very rarely - optic neuritis / optic neuropathy;
• Nervous system: often - nightmares, sleep disturbances, tremors or other extrapyramidal symptoms; infrequently - sensorimotor peripheral neuropathies and / or myopathy; rarely - headache, cerebellar ataxia, benign intracranial hypertension;
• Genital organs and mammary gland: very rarely - impotence, epididymitis;
• Hematopoietic system: very rarely - hemolytic and aplastic anemia, thrombocytopenia;
• Skin and subcutaneous tissues: very often - photosensitivity; often (with prolonged use of the drug in high doses) - bluish or grayish pigmentation of the skin (slowly disappears after stopping therapy); very rarely - alopecia, skin rash, exfoliative dermatitis, erythema (during radiation therapy); with an unknown frequency - urticaria;
• Laboratory and instrumental data: very rarely - an increase in the concentration of creatinine in the blood serum;
• Allergic reactions: with an unknown frequency - angioedema;
• General disorders: with an unknown frequency - the formation of granulomas, including bone marrow granuloma.

• Cardiovascular system: often - a decrease in blood pressure, usually moderate and transient, bradycardia (usually a moderate decrease in heart rate); very rarely - arrhythmogenic effect; with an unknown frequency - ventricular tachycardia of the pirouette type;
• Endocrine system: with an unknown frequency - hyperthyroidism;
• Respiratory system: very rarely - acute respiratory distress syndrome (sometimes fatal), interstitial pneumonitis, shortness of breath, cough, apnea and / or bronchospasm;
• Digestive system: very rarely - nausea;
• Liver and biliary tract: very rarely - an isolated increase in liver transaminase activity in the blood serum (usually moderate), within 24 hours after administration of amiodarone - acute liver damage, with jaundice and / or an increase in transaminases, including the development of liver failure, sometimes with a fatal outcome ;
• Skin and subcutaneous tissues: very rarely - increased sweating, a feeling of heat; with an unknown frequency - urticaria;
• Nervous system: very rarely - headache, benign intracranial hypertension;
• The immune system: very rarely - anaphylactic shock; with an unknown frequency - Quincke's edema;
• Musculoskeletal system: with an unknown frequency - pain in the lumbar and lumbosacral spine;
• Local reactions: often - swelling, pain, pigmentation, infiltration, erythema, inflammation, necrosis, thrombophlebitis, extravasation, induration, phlebitis, infection, cellulitis (reactions at the injection site).

special instructions

Due to the fact that the side effects of amiodarone are dose-dependent, it is recommended to use the drug in the lowest effective doses in order to minimize the possibility of their occurrence.

During treatment, patients should avoid exposure to direct sunlight or take appropriate protective measures (use sunscreen, etc.).

• Conduct an ECG and determine the content of potassium in the blood;
• Correct hypokalemia, if any;
• Conduct laboratory and clinical examination to identify diseases and disorders of the thyroid gland;
• Check for proper functioning of a pacemaker or implanted defibrillator in patients receiving long-term therapy for arrhythmias.

Before surgery, the anesthesiologist should be informed that the patient is taking Kordaron.

drug interaction

Amiodarone has a high pharmacological activity, in this regard, only the attending physician can take into account drug interaction Cordarone with drugs taken simultaneously with it.

Terms and conditions of storage

Keep out of the reach of children, dry and protected from light: solution at temperatures up to 25 ° C; tablets - up to 30 ° C.

The shelf life of the solution is 2 years; tablets - 3 years.

• Instructions for use Kordaron ®
• Composition of Cordaron ®
• Indications for Kordaron ®
• Storage conditions of the drug Kordaron ®
• Shelf life of Cordaron ®

ATC code: Cardiovascular system (C) > Cardiac medicines (C01) > Class I and III antiarrhythmic drugs (C01B) > Class III antiarrhythmic drugs (C01BD) > Amiodarone (C01BD01)

Release form, composition and packaging

tab. divisible 200 mg: 30 pcs.
Reg. No: 8805/08/13 dated 10/31/2013 - Valid

Divisible tablets from white to yellowish white, round, with a dividing line and an engraving of the symbol in the form of a heart and "200" on one of the sides.

Excipients: lactose monohydrate - 71 mg, corn starch - 66 mg, polyvidone K90F (E1201) - 6 mg, colloidal anhydrous silicon dioxide (E551) - 2.4 mg, magnesium stearate (E470) - 4.6 mg.

10 pieces. - blisters (3) - packs of cardboard.

Description medicinal product CORDARON ® based on the officially approved instructions for use of the drug and made in 2013. Date of update: 06/19/2014

pharmachologic effect

Class III antiarrhythmic drug. It has antiarrhythmic and antianginal effects.

Antiarrhythmic action due to the lengthening of the 3rd phase of the action potential of cardiomyocytes without changing its height or rate of rise (class III according to the classification of Vaughan Williams). Isolated lengthening of the 3rd phase of the action potential occurs due to the slowing down of potassium currents, without changing the currents of sodium or calcium. In addition, the drug reduces the automatism of the sinus node to bradycardia, which does not respond to the effects of atropine. Non-competitively blocks α- and β-adrenergic receptors. Slows down conduction in the sinoatrial node, atria and
AV node, which is more pronounced with an accelerated rhythm. Does not change intraventricular conduction. Increases the refractory period and reduces myocardial excitability at the atrial, AV-nodal and ventricular levels. Slows down conduction and lengthens the refractory period of accessory atrioventricular pathways.

Antianginal (anti-ischemic) action due to a moderate decrease in peripheral vascular resistance and a decrease in heart rate, which leads to a decrease in oxygen consumption. It also non-competitively blocks α- and β-adrenergic receptors. Increases coronary blood flow due to a direct effect on the smooth muscles of the myocardial arteries. Maintains cardiac output by reducing intra-arterial pressure and OPSS. Amiodarone does not have a significant negative inotropic effect.

The therapeutic effect develops on average within 1 week (from several days to 2 weeks).

Pharmacokinetics

Suction

The absorption of amiodarone is slow and variable, the drug has a high affinity for tissues. Bioavailability after oral administration ranges from 30% to 80% (average 50%). C max in plasma after taking a single dose is observed after 3-7 hours.

Distribution

The volume of distribution is very large, but varies individually, since amiodarone actively accumulates in tissues (adipose tissue, liver, lungs, spleen).

Metabolism

Amiodarone is metabolized primarily by CYP3A4 and also by CYP2C8. Amiodarone and its metabolite, deethylamiodarone, have the ability to inhibit CYP 2C9, CYP 2C19, CYP 2D6, CYP 3A4, CYP 2A6, CYP 2B6 and 2C8 in vitro. Amiodarone and deethylamiodarone also have the ability to inhibit certain transport systems, such as P-glycoprotein and organic cation transporter (OCT2). (In one study, an increase in creatinine concentration (substrate of OCT 2) by 1.1% was noted. Data from in vitro studies provide information on interactions with CYP 3A4, CYP 2C9, CYP 2D6 and P-glycoprotein substrates.

breeding

Amiodarone has a long T 1/2 that varies individually (from 20 to 100 days). During the first few days of treatment, amiodarone accumulates in most body tissues, especially adipose tissue. Elimination begins after a few days, and C ss is reached after 1 or several months, depending on the individual response of the patient. Due to these properties, in order to quickly achieve the concentrations in the tissues necessary for the manifestation of a therapeutic effect, loading doses of the drug should be used.

A dose of amiodarone 200 mg contains 75 mg of iodine. The iodine group is separated from the molecule and enters the urine in the form of iodides. This corresponds to 6 mg/24 hours of free iodine for daily dose amiodarone 200 mg.

Amiodarone is excreted mainly with bile and feces. Renal excretion is negligible, which allows the use of standard doses in patients with renal insufficiency. After discontinuation of treatment, the excretion of the drug continues for several months; it should be noted that the pharmacodynamic effect persists for a period of 10 days to one month.

Neither amiodarone nor its metabolites can be removed by dialysis.

Controlled pediatric studies have not been conducted. In the limited published data on pediatric patients, differences from adults have not been noted.

Indications for use

• prevention of recurrence of life-threatening ventricular tachycardia (treatment should be started in a hospital with careful cardiac monitoring);
• prevention of recurrence of ECG-confirmed, symptomatic and disabling ventricular tachycardia;
• prevention of recurrence of ECG-confirmed supraventricular tachycardia with established need for treatment, if the tachycardia is resistant to other methods of treatment, or there are contraindications to the use of other drugs;
• prevention of recurrence of ventricular fibrillation;
• prevention of rhythm disturbances in Wolff-Parkinson-White syndrome;
• treatment of atrial fibrillation: slowing the heart rate or restoring sinus rhythm with flutter or atrial fibrillation (fibrillation);

Amiodarone may be used in the presence of CAD and/or left ventricular dysfunction.

• prevention of deaths due to arrhythmias in patients at high risk of symptomatic congestive heart failure or recent myocardial infarction against a background of low ejection fraction or asymptomatic ventricular extrasystoles;

Amiodarone is indicated for the prevention of all-cause mortality, including sudden cardiac arrest. deaths in high-risk patients with congestive heart failure of an ischemic or non-ischemic nature. High risk is generally defined as having clinical symptoms severe heart failure or a decrease in the ejection fraction from the left ventricle below 40% of the norm with or without signs of ventricular arrhythmia.

Dosing regimen

The drug is administered orally adults.

Initial treatment: the initial dosing regimen (loading dose) is 600 mg (3 tablets) / day for 8-10 days. In some cases, at the beginning of treatment, higher doses are used - 800-1000 mg (4-5 tablets) per day, but only for a short time and under ECG control. The result of therapeutic saturation are characteristic changes in the ECG:

• prolongation of the QT interval (due to the prolongation of the repolarization period) with the possible appearance of a U wave.

Supportive care: the minimum effective dose should be selected, which, in accordance with the individual response of the patient, can be in the range from 100 mg (1/2 tab.) / day (or 1 tab. every other day) to 400 mg (2 tab.) / day daily. During treatment, regular monitoring of the ECG is necessary.

At patients with renal insufficiency dose adjustment is not required, but there is no clinical experience.

Clinical experience with patients with impaired liver function missing.

At elderly patients data on the use of the drug is not enough, amiodarone should be used with extreme caution.

The safety and efficacy of amiodarone in children not installed. Controlled pediatric studies have not been conducted. In published studies, the safety of amiodarone was evaluated in 1118 pediatric patients with a variety of arrhythmias. In pediatric clinical research the following doses have been used:

• loading dose - 10-20 mg / kg / day for 7-10 days (or 500 mg / m 2 / day), maintenance dose (minimum effective dose), depending on the individual response, it can vary from 5 to 10 mg / kg / day (or 250 mg / m 2 / day).

Side effects

Side effects were classified by organs and systems, as well as by the frequency of manifestation as follows:

• very often (≥1/10);
• often (≥1/100 to<1/10);
• infrequently (≥1/1000 to<1/100);
• rare (≥1/10,000 to<1/1000);
• rarely (<1/10 000), частота неизвестна (не может быть оценена на основе имеющихся данных).

From the side of the organ of vision: very common - micro-deposits on the cornea, almost always present in adults, are usually limited to the area under the pupil and do not require discontinuation of treatment. They rarely lead to visual impairment in the form of a colored halo in bright light or a foggy feeling. Corneal microdeposits consist of complex lipid components and are always completely reversible after discontinuation of the drug;

very rarely - several cases of neuropathy / neuritis of the optic nerve with blurring, decreased visual acuity and swelling of the fundus have been described. This can lead to a more or less severe reduction in visual acuity. The relationship of this phenomenon with amiodarone has not yet been established, however, in the absence of other obvious reasons, treatment with the drug should be suspended.

From the side of the skin: very often - photosensitivity (patients should be warned to avoid sunlight and UV rays in general during treatment);

often - grayish or bluish pigmentation of the skin (after stopping treatment, this pigmentation slowly (within 10-24 months) disappears);

very rarely - during radiotherapy, cases of erythema may occur, there are reports of skin rashes, usually of low specificity, isolated cases of exfoliative dermatitis (however, the connection with the drug has not been established), hair loss;

frequency unknown - urticaria.

From the endocrine system: often - hypothyroidism, hyperthyroidism, sometimes fatal, syndrome of inappropriate ADH secretion.

From the side of the respiratory system: often - cases of pulmonary toxicity (alveolar / interstitial pneumonitis and bronchiolitis obliterans with pneumonia) are described, sometimes with a fatal outcome. In patients with developing dyspnea or non-productive cough, both independent symptoms and worsening general condition (fatigue, weight loss, fever), a chest x-ray should be performed and, if necessary, the drug should be discontinued. These types of pneumopathy can lead to pulmonary fibrosis, but they are mostly reversible with early withdrawal of amiodarone with or without corticosteroids. Clinical symptoms usually disappear within 3-4 weeks, and then there is a slower recovery of the radiological picture and lung function (several months). There have been cases of pleurisy associated with interstitial pneumopathies. There are also cases of pulmonary hemorrhage (occurrence unknown);

very rarely - several cases of bronchospasm have been described, especially in patients with bronchial asthma, several cases of acute respiratory syndrome have been described, sometimes ending in death, most often immediately after surgery (the influence of high oxygen concentration during mechanical ventilation is possible).

From the nervous system: often - tremor or other extrapyramidal symptoms, sleep disturbances, incl. nightmares, sensory, motor or mixed peripheral neuropathies;

infrequently - myopathies (peripheral sensorimotor neuropathies and / or myopathies may develop only after several months, sometimes after several years of treatment. They are usually reversible after discontinuation of the drug. However, recovery may be incomplete, very slow and appear only a few months after discontinuation) ;

very rarely - cerebellar ataxia, benign intracranial hypertension, headaches (the appearance of headaches requires examination to determine the causes.

From the side of the liver: liver dysfunction was noted, manifested in an increased level of serum transaminases:

• very often - an isolated and usually moderate (1.5-3 times higher than normal values) increase in the level of transaminases;
• decreases with dose reduction or even spontaneously;
• often - acute hepatopathy with elevated serum transaminases and / or jaundice, among which there were deaths (in such cases, treatment should be discontinued);
• very rarely - there are reports of chronic hepatitis with long-term treatment. The histology is consistent with pseudo-alcoholic hepatitis. Clinical symptoms and laboratory changes may be minimal (non-permanent hepatomegaly, transaminase levels elevated up to 1.5-5 times normal);
• therefore, regular monitoring of liver function is recommended during treatment. Even a moderate increase in transaminase levels observed after treatment lasting more than 6 months may indicate chronic hepatic disorders. Clinical and biological abnormalities usually regress after discontinuation of the drug;
• however, there are several reports of irreversible changes.

From the side of the heart: often - mostly moderate and dose-dependent bradycardia;

not often - conduction disturbances (sinoatrial blockade, AV blockade of various degrees);

very rarely - in some cases (sinus node dysfunction, elderly patients), severe bradycardia is described or, in exceptional cases, stop of the sinus node;

the frequency is unknown - tachycardia of the "pirouette" type.

From the gastrointestinal tract: very often - benign gastrointestinal disorders (nausea, vomiting, taste disturbances), usually occur at the beginning of treatment and disappear when the dose is reduced.

From the reproductive system: very rarely - epididymitis, impotence.

From the vascular side: very rarely - vasculitis.

From laboratory and instrumental studies: very rarely - kidney dysfunction with a moderate increase in creatinine levels.

From the blood and lymphatic system: very rarely - thrombocytopenia, hemolytic anemia, aplastic anemia.

From the immune system: the frequency is unknown - angioedema (Quincke's edema).

Contraindications for use

• sinus bradycardia and sinoatrial blockade (except for cases of correction by an artificial pacemaker);
• SSSU, with the exception of cases of correction by an artificial pacemaker (danger of stopping the sinus node);
• severe conduction disturbances (in the absence of condition correction by an artificial pacemaker);
• hyperthyroidism (due to the possible aggravation of the condition by amiodarone);
• simultaneous use of drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type: class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide), class III antiarrhythmic drugs (sotalol, dofetilide, ibutilide), sultopride, other drugs (bepridil, cisapride, difemanil, in /in erythromycin, mizolastine, moxifloxacin, IV vincamine);
• pregnancy;
• lactation period (breastfeeding);
• hypersensitivity to amiodarone, iodine or any of the excipients.

Use during pregnancy and lactation

Pregnancy

In animal studies, the drug had a fetotoxic effect in some species. Reception of amiodarone in the II and III trimester of pregnancy and especially before childbirth is associated with a risk; the drug can cause bradycardia and prolongation of the QT interval in newborns and impair thyroid function in the fetus. Therefore, amiodarone therapy during pregnancy is contraindicated unless the benefit outweighs the risk.

Breast-feeding

Amiodarone is excreted in significant amounts in breast milk, and therefore the use of the drug during breastfeeding is contraindicated.

Fertility

Data on the effect on fertility in humans are not available.

Use in elderly patients

In elderly patients, data on the use of the drug is not enough, amiodarone should be used with extreme caution.

In elderly patients, heart rate may decrease more pronouncedly.

special instructions

Before starting treatment, an ECG should be performed. In elderly patients, heart rate may decrease more pronouncedly. The pharmacological action of amiodarone causes changes in the ECG:

• prolongation of the QT interval (due to prolongation of repolarization) with the possible appearance of a U wave;
• these changes are the result of therapeutic saturation, not toxicity.

The drug should be discontinued in case of development of AV block II and III degree, sinoatrial block or bifascicular block. In case of development of AV-blockade of the I degree it is necessary to strengthen supervision. There are reports of the emergence of new types of rhythm disturbances or the aggravation of previously existing ones. The arrhythmogenic effect of amiodarone is insignificant, less than that of most antiarrhythmic drugs, and usually occurs in combination with certain drugs or in electrolyte imbalance.

Amiodarone contains iodine and therefore may interfere with the results of some tests used to evaluate thyroid function (radioactive iodine binding, PBI). However, thyroid function can be monitored by determining the level of blood hormones (T3, T4, TSH). Amiodarone may cause thyroid dysfunction, especially in patients with a history of thyroid dysfunction. Therefore, before starting treatment, regularly (for example, every 6 months) during treatment, and several months after the end of treatment, serum TSH levels should be measured. If thyroid dysfunction is suspected during treatment with amiodarone, TSH levels should also be measured.

Bouts of dyspnea or dry cough may be associated with pulmonary toxicity, such as the development of interstitial pneumonitis. Patients who experience episodes of dyspnea after exercise as the only symptom or in the context of a deterioration in the patient's general condition (fatigue, weight loss and fever) should have a chest x-ray. Continued treatment with amiodarone should be considered because interstitial pneumonitis is often reversible with early discontinuation of amiodarone (clinical symptoms resolve within 3-4 weeks, radiological changes and improvement in lung function are seen within a few months). The possibility of using corticosteroids should be evaluated. In very rare cases, severe respiratory complications, sometimes with a fatal outcome (acute respiratory failure syndrome in adults), have been noted, usually after surgery. These complications may develop due to interactions associated with high oxygen concentrations.

Regular monitoring of liver function is recommended at the beginning and during treatment with amiodarone. . With oral therapy, acute (severe hepatocellular liver failure or liver damage, sometimes fatal) or chronic liver dysfunction may develop; in this regard, it is recommended to reduce the dose of amiodarone or stop treatment with the drug if the level of transaminases exceeds the norm by more than 3 times. Clinical and biological symptoms of chronic liver failure with oral therapy may be mild in severity (enlargement of the liver, elevated transaminase levels 5 times higher than normal) and reversible upon discontinuation of drug treatment, but deaths have also been reported.

Amiodarone can cause sensory, motor, or mixed peripheral neuropathies and myopathies. . Resolution of symptoms is usually observed within a few months after discontinuation of amiodarone treatment, however, some symptoms may persist.

If vision is blurred or visual acuity is reduced, a complete ophthalmologic examination, including fundus examination, should be performed promptly. In case of development of neuropathy or optic neuritis caused by amiodarone, the drug must be discontinued, as there is a possibility of blindness.

Combination with beta-adrenergic blockers other than sotalol is contraindicated; combination with esmolol requires caution when using.

Combination with verapamil or diltiazem should only be used to prevent life-threatening ventricular arrhythmias.

Since the drug contains lactose, it is contraindicated in patients with congenital galactosemia, glucose-galactose malabsorption syndrome or lactase deficiency.

Side effects , are generally dose dependent and therefore the lowest effective therapeutic dose should be used. Patients should be advised to avoid sunlight and use sun protection measures during treatment.

In addition, since amiodarone can lead to hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disorders, it is recommended to start clinical and biological monitoring of TSH before using amiodarone. This monitoring should be continued during treatment and for several months after its termination. If thyroid dysfunction is suspected, serum TSH levels should be measured.

Cases of increased ventricular defibrillation and/or pacing threshold of a pacemaker or an implantable electrical heart defibrillator have been reported, potentially affecting the effectiveness of the drug, especially in the context of long-term use of antiarrhythmic drugs. In this regard, before and during treatment with amiodarone, a periodic check of the operation of the device used should be performed.

Amiodarone contains iodine and therefore may interfere with radioiodine intake. However, thyroid function test results (free T3, free T4, TSH) remain interpretable. Amiodarone inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and can cause local biochemical changes in patients with normal thyroid function (increased levels of free T4 against a background of a slight decrease or even maintenance of normal levels of free T3). Such phenomena do not require discontinuation of treatment with amiodarone.

The basis for suspicion of hypothyroidism is the development of the following clinical symptoms:

• weight gain, cold intolerance, reduced activity, excessive bradycardia. The diagnosis is confirmed by a marked increase in serum TSH levels. Recovery of thyroid function to normal usually occurs within 1-3 months after discontinuation of therapy. In life-threatening cases, amiodarone therapy may be continued in combination with levothyroxine. The dose of levothyroxine is adjusted according to the TSH level.

Before surgery, the anesthesiologist should be notified that the patient is taking amiodarone.

The medicinal product contains lactose monohydrate (71 mg). The drug should not be taken by patients with hereditary lactose intolerance, galactose intolerance or malabsorption of glucose-galactose.

Pediatric use

The efficacy and safety of amiodarone in children has not been established, therefore, the use of the drug in pediatric patients is not recommended.

Influence on the ability to drive vehicles and control mechanisms

The ability to drive vehicles or other mechanisms may be impaired in the event of violations of the organ of vision as a result of taking amiodarone.

Overdose

Little information is available regarding the administration of high doses of amiodarone. Several cases of sinus bradycardia, attacks of ventricular tachycardia, in particular torsades de pointes, and liver damage have been described.

Treatment should be symptomatic. Taking into account the pharmacokinetic profile of the drug, it is recommended to monitor the patient's condition for a sufficiently long time, especially heart rate monitoring is important. Neither amiodarone nor its metabolites are removed during dialysis.

drug interaction

Simultaneous appointment drugs that can cause torsades de pointes arrhythmia contraindicated:

• class IA antiarrhythmics, sotalol, bepridil, as well as non-antiarrhythmic drugs such as vincamine, sultopride, IV erythromycin, pentamidine (for parenteral use).

Co-administration of amiodarone with drugs that prolong the QT interval should be based on a careful assessment of the possible benefits and risks for each patient, since the risk of developing torsades de pointes may increase, and patients should be monitored for QT prolongation.

Prescribing should be avoided fluoroquinolones in patients receiving amiodarone.

• simultaneous appointment with drugs that reduce heart rate or cause disturbances in automatism or conduction: beta-blockers and calcium channel blockers(verapamil, diltiazem), since automatism disorders (excessive bradycardia) and conduction may develop;
• simultaneous appointment with drugs that can cause hypokalemia: stimulant laxatives, because the risk of developing arrhythmia of the "pirouette" type increases; other types of laxatives should be used.

Should be careful when using the following medicines in combination with Kordaron:

• diuretics that cause hypokalemia (monopreparations and combined preparations);
• systemic corticosteroids (gluco- and mineralocorticoids), tetracosactide;
• amphotericin B (i.v.). It is necessary to prevent the development of hypokalemia and correct it if it occurs. The QT interval should be monitored, and antiarrhythmic drugs should not be prescribed in the case of torsades de pointes (ventricular pacing should be started, IV magnesium may be used).

Potentially serious complications have been reported in patients undergoing general anesthesia:

• bradycardia (resistant to atropine), hypotension, conduction disturbances, decreased cardiac output. In very rare cases, severe complications from the respiratory system (acute adult respiratory distress syndrome) have been observed, sometimes fatal, as a rule, immediately in the postoperative period. A possible relationship with a high oxygen concentration can be assumed.

Effect of amiodarone on other medicinal products

Amiodarone and/or its metabolites, deethylamiodarone, inhibit CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein and may increase exposure to their substrates. Due to the long half-life of amiodarone, interactions may occur for several months after discontinuation of amiodarone.

Amiodarone is a P-glycoprotein inhibitor. It is expected that concurrent use with P-glycoprotein substrates will increase their impact.

digitalis preparations a violation of automatism (excessive bradycardia) and AV conduction (synergistic effect) may develop; in addition, an increase in the concentration of digoxin in plasma is possible due to a decrease in the clearance of digoxin. ECG and plasma concentrations of digoxin should be monitored; and patients should be monitored for clinical signs of toxicity from digitalis preparations. It may be necessary to adjust the therapeutic dose of cardiac glycosides.

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 according to its indication.

CYP2C9 substrates such as warfarin or phenytoin by inhibiting CYP2C9. Combination warfarin with amiodarone may enhance the effect of an oral anticoagulant, thereby increasing the risk of bleeding. It is necessary to more regularly monitor the level of prothrombin and adjust the dose of oral anticoagulants both during treatment with amiodarone and after stopping treatment with amiodarone. Combination phenytoin with amiodarone can lead to an overdose of phenytoin with the development of neurological manifestations. Clinical monitoring should be carried out and the dose of phenytoin should be reduced as soon as signs of overdose appear; it is necessary to control the concentration of phenytoin in plasma.

Amiodarone increases concentration flecainida in plasma by inhibiting cytochrome CYP2D6. Therefore, the dose of amiodarone should be reduced.

When drugs that are CYP3A4 substrates co-administered with amiodarone, a CYP3A4 inhibitor, this may lead to higher plasma concentrations, which may cause an increase in their toxicity:

• combination cyclosporine with amiodarone may plasma concentrations of cyclosporine, so the dose should be adjusted;
• combination fentanyl with amiodarone may increase the pharmacological effects of fentanyl and increase the risk of its toxicity;
• with concomitant use of amiodarone with statins metabolized by CYP3A4, such as simvastatin, atorvastatin and lovastatin increases the risk of muscle toxicity. For appointment with amiodarone, it is recommended to use statins that are not metabolized by CYP3A4,
• other drugs metabolized by CYP3A4: lidocaine, tacrolimus, sildenafil, midazolam, triazolam, dihydroergotamine, ergotamine, colchicine.

When used simultaneously with drugs with a negative inotropic effect, causing bradycadia, and / or depressing the AV node, monitoring of clinical manifestations and ECG is necessary.

Simultaneous use with antiarrhythmic drugs of various groups may be helpful, but requires careful monitoring and ECG verification.

Effect of other medicinal products on amiodarone

CYP3A4 inhibitors and CYP2C8 inhibitors have the potential to inhibit the metabolism of amiodarone and increase its exposure.

Contacts for appeals

SANOFI-AVENTIS GROUP, representative office, (France)

Representation in the Republic of Belarus
Joint Stock Company "Sanofi-Aventis Groupe"