Instructions for use CORDARON, p-d/injections

Pharmacological properties of the drug Cordarone

Class III antiarrhythmic agent. The mechanism of action of amiodarone is due to the blockade of ion channels of the cell membranes of cardiomyocytes (mainly potassium, to a very small extent - calcium and sodium), as well as non-competitive suppression of α- and β-adrenergic activity. As a class III antiarrhythmic agent (according to the Vaughan Williams classification), it increases the 3rd phase of the action potential. Slows down conduction in the sinoatrial, AV node and atria, especially at high heart rates. Does not change intraventricular conduction. Increases the refractory period and reduces the excitability of the myocardium of the atria, ventricles and AV node. The antianginal effect of the drug is due to a decrease in myocardial oxygen demand (due to a decrease in heart rate and a decrease in afterload) and an increase in coronary blood flow due to a direct effect on the smooth muscles of the coronary arteries. Supports cardiac output by reducing aortic pressure and peripheral vascular resistance. With intravenous administration, maximum activity is achieved after 15 minutes and lasts up to 4 hours. After oral administration, amiodarone is absorbed slowly, the pharmacokinetics are characterized by significant individual fluctuations. Amiodarone has a very large and variable volume of distribution due to extensive accumulation in various tissues (adipose tissue, heavily perfused organs such as the liver, lungs and spleen). Bioavailability when taken orally ranges from 30–80% (on average about 50%). After a single dose, the maximum concentration in the blood plasma is reached after 3–7 hours. The therapeutic effect is usually observed 1 week after the start of therapy (from several days to 2 weeks). Amiodarone has a long half-life (20–100 days). In the first days of treatment, the drug accumulates in almost all tissues, especially in adipose tissue. Elimination begins within a few days and steady-state plasma concentrations are achieved within one or several months. Taking into account the pharmacokinetics, obtaining a therapeutic effect requires the use of an initial saturating dose in order to achieve drug accumulation in tissues. 200 mg of amiodarone contains 75 mg of iodine, 6 mg of which is released as free iodine. Amiodarone is primarily excreted in bile and feces. Excretion in urine is insignificant, which allows the drug to be prescribed in normal doses to patients with renal failure. After discontinuation of the drug, its removal from the body continues for several months; It should be taken into account that after discontinuation of the drug, its effect lasts from 10 days to 1 month.

Pharmacodynamics and pharmacokinetics

The main substance is amiodarone . It has coronary dilation, antianginal, hypotensive, alpha-adrenergic blocking, beta-adrenergic blocking effects. Under the influence of the drug, the oxygen demand of the heart muscle decreases, which explains the antianginal effect . Cordarone inhibits the functioning of alpha and beta adrenergic receptors of the cardiovascular system without blocking them.

Amiodarone reduces the sensitivity of the sympathetic nervous system to hyperstimulation, reduces the tone of the coronary arteries, improves blood flow, slows down the pulse, increases the energy reserves of the myocardium, and lowers blood pressure.

The antiarrhythmic effect is achieved by influencing the course of electrophysiological processes in the myocardium, lengthening the action potential of myocardiocytes, increasing the refractory, effective period of the atria, His bundle, AV node, and ventricles.

Cordarone is able to inhibit diastolic, slow depolarization of the cell membrane of the sinus node, inhibit atrioventricular conduction, and cause bradycardia . The structure of the main component of the drug is similar to thyroid hormone.

Indications for use of the drug Cordarone

Prevention of relapses of ventricular tachycardia or ventricular fibrillation, which pose a danger to the patient’s life (treatment begins in the hospital); symptomatic and disabling documented ventricular tachycardia; documented supraventricular tachycardia in patients with heart disease; other rhythm disturbances if other antiarrhythmic drugs are ineffective or contraindicated; rhythm disturbances in WPW syndrome. Treatment of documented supraventricular tachycardia to control heart rate during atrial fibrillation or flutter, especially in patients with coronary artery disease and/or functional dysfunction of the left ventricle. Prevention of lethal arrhythmias in patients at high risk associated with congestive heart failure or recent myocardial infarction with low ejection fraction or asymptomatic ventricular extrasystoles.

Use of the drug Cordarone

IV administration IV administration Cordarone is prescribed if a quick effect is needed or if it is impossible to take the drug orally. Cordarone can only be administered in an isotonic (5%) glucose solution. The drug should not be diluted with isotonic sodium chloride solution, since the formation of a precipitate is possible. The contents of 2 ampoules of the drug must be diluted in at least 500 ml of glucose solution. Do not mix with other drugs. Before infusion, Cordarone solution should be diluted in systems that do not contain 2-diethylhexyl phthalate (for example, PVC, polyethylene, polypropylene, glass), since Cordarone solution may release 2-diethylhexyl phthalate. Injected only into the central veins. The loading dose for intravenous infusion is usually 5 mg/kg and is administered only in glucose solution over 20 minutes to 2 hours. Administration can be repeated 2-3 times within 24 hours. The infusion rate should be adjusted taking into account the therapeutic effect. The therapeutic effect of the drug appears during the first minutes of administration and then gradually decreases after its completion, so a maintenance infusion is necessary. The maintenance dose is 10–20 mg/kg per day (on average 600–800 mg/day, maximum dose 1200 mg/day) in 250 ml of glucose solution for several days. From the first day of infusion, it is necessary to begin the transition to oral administration of the drug (3 tablets of 200 mg per day). If necessary, the dose can be increased to 4–5 tablets per day. For children over 3 years of age, the recommended dose is 5 mg/kg. The drug can only be used under close medical supervision. The regimen for taking the drug is determined individually. Oral administration Loading dose Various regimens can be used, usually the initial dose is 600-1000 mg/day for 8-10 days. Maintenance dose The minimum effective dose should be used. Depending on the patient’s response to the use of the drug, the maintenance dose can range from 100 mg to 400 mg/day. Since Cordarone has a very long half-life, it can be taken every other day at a dose of 200 mg or daily at a dose of 100 mg. You can take breaks from taking Cordarone 2 times a week.

Cordarone price, where to buy

The price of Cordarone in 200 mg tablets is 320 rubles per pack of 30 pieces.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine
• Online pharmacies in KazakhstanKazakhstan

LuxPharma* special offer

• Cordarone tab.
  200 mg No. 30 1700 rub. order

Pharmacy Dialogue

• Cordarone (200 mg tablet No. 30)Chinoin

  RUB 194 order

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Pharmacy24

• Cordarone 200 mg No. 30 tablets Quinoin Pharmaceutical and Chemical Products Plant Private Co. Ltd., Ugorshchina
  204 UAH.order
• Cordarone 150 mg 50 mg/ml 3 ml No. 6 injection solution Sanofi Vinthrop Industries, France

  219 UAH. order

PaniPharmacy

• Cordarone ampoule Cordarone solution d/in. 150mg amp. 3ml No. 6 France, Sanofi Winthrop Industrie

  225 UAH order

• Cordarone tablets Cordarone tablets. 200 mg No. 30 France, Sanofi Winthrop Industrie

  206 UAH order

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Contraindications to the use of the drug Cordarone

Sinus bradycardia (in the absence of pacemaker correction), sick sinus syndrome (in the absence of pacemaker correction), sinoatrial block, AV block and bundle branch block (in the absence of a pacemaker), severe arterial hypotension, vascular insufficiency, hyperthyroidism, hypersensitivity to amiodarone or iodine, II–III trimester of pregnancy and breastfeeding, age up to 3 years. Concomitant use with drugs that can cause paroxysmal ventricular tachycardia such as torsade de pointes is contraindicated.

Contraindications

Cordarone is not prescribed for sinus bradycardia , iodine intolerance, amiodarone, cardiogenic shock , collapse, hypokalemia, hypothyroidism , arterial hypotension, breastfeeding, interstitial lung diseases, pregnancy, taking MAO inhibitors, hypokalemia, 2-3 degree atrioventricular block.

Elderly people, with liver pathology, heart failure, patients under 18 years of age, with pathology of the hepatic system are prescribed with caution.

Side effects of the drug Cordarone

bradycardia (mostly moderate and dose-dependent), sometimes (with sinus node dysfunction, in elderly patients) - severe bradycardia and extremely rarely - cardiac arrest. Conduction disturbances are rarely observed (sinoatrial block, atrioventricular block of varying degrees). In some cases, an arrhythmogenic effect is noted, in some cases with subsequent cardiac arrest. There is currently no data on whether this is caused by the drug or related to underlying heart disease or lack of response to therapy. These effects are recorded less frequently than with most other antiarrhythmic drugs and are observed mainly during interactions with certain drugs or in cases of electrolyte imbalance. Microdeposits are often noted on the retina of the eye, usually in the area under the pupil, which sometimes cause a hazy or colored halo sensation in glare. Microdeposits on the retina consist of complex fatty layers, disappear after discontinuation of the drug and do not require cessation of treatment. In some cases, neuropathy/optic neuritis is noted, but their connection with taking Cordarone has not been established. Since optic neuropathy can lead to blindness, if blurred or decreased visual acuity occurs, it is recommended to conduct a full ophthalmological examination, including diaphanoscopy, and reconsider the need for treatment with Cordarone. Photosensitivity may occur, so patients should be warned that during treatment it is necessary to avoid insolation and ultraviolet irradiation. Erythema may occur during radiotherapy. In some cases, a skin rash may be observed, usually non-specific, sometimes exfoliative dermatitis. However, their cause-and-effect relationship with taking Cordarone has not been proven. With prolonged use of the drug in high doses, grayish or bluish pigmentation of the skin may be observed; After stopping treatment, this pigmentation slowly disappears. Due to the presence of iodine in the drug molecule, a change in biochemical parameters characterizing the function of the thyroid gland is often observed - an increase in the level of T4 with a normal or slightly reduced level of T3. In the absence of clinical signs of thyroid dysfunction, discontinuation of the drug is not required. Hypothyroidism is possible, clinical symptoms (usually mild) of which may include weight gain, decreased activity, and bradycardia that is excessive compared to the expected effect of Cordarone. The diagnosis is confirmed by an increase in the level of thyroid-stimulating hormone in the blood serum. A euthyroid state is usually achieved 1–3 months after cessation of treatment. In life-threatening situations, treatment with Cordarone can be continued simultaneously with the prescription of levothyroxine, the dose of which is determined depending on the level of thyroid stimulating hormone. Hyperthyroidism may occur during treatment and for several months after discontinuation of the drug. Clinical symptoms (usually mild) of hyperthyroidism can be: weight loss, the appearance of arrhythmia, angina pectoris, congestive heart failure. The diagnosis is confirmed by a clear decrease in the level of thyroid-stimulating hormone in the blood serum. In this case, Cordarone must be discontinued. Recovery usually occurs within several months after discontinuation of the drug, clinical recovery precedes the normalization of biochemical indicators of thyroid function. In severe cases, which can be fatal, emergency treatment is required. Depending on the specific clinical situation, antithyroid drugs, corticosteroids, and β-adrenergic receptor blockers are prescribed. An isolated increase in transaminase activity in the blood serum at the beginning of treatment is usually moderate (1.5–3 times higher than normal), normalizes after reducing the dose of the drug or spontaneously. In some cases, acute impairment of liver function with high levels of transaminases in the blood serum and/or jaundice may occur, requiring discontinuation of the drug (otherwise death is possible). Pseudoalcoholic hepatitis and cirrhosis may occur. Clinical symptoms and changes in laboratory tests may be minimally pronounced (hepatomegaly, transaminase activity increased by 1.5–5 times compared to normal levels). Therefore, regular monitoring of liver function is recommended during treatment. The severity of clinical and biochemical manifestations usually decreases after discontinuation of the drug, but death is also possible. In some cases, pulmonary toxicity may occur: alveolar/interstitial pneumonitis or fibrosis, pleurisy, bronchiolitis obliterans with pneumonia, sometimes fatal. In patients with developing dyspnea (during exertion), either isolated or with a deterioration in general condition (fatigue, decreased body weight, increased body temperature), a chest x-ray should be performed. Pulmonary disorders are mostly reversible with early discontinuation of Cordarone. Clinical symptoms usually disappear within 3–4 weeks, followed by a slower recovery of radiographic appearance and pulmonary function (over several months). Therefore, the need for treatment with Cordarone should be reconsidered and, if necessary, GCS should be prescribed. In patients with severe respiratory disorders and especially in patients with asthma, bronchospasm may develop in some cases. In some cases, acute respiratory distress syndrome may occur in adults, sometimes with a fatal outcome, most often immediately after surgery (possible incompatibility with high oxygen concentrations). Rarely, peripheral sensorimotor neuropathy and/or myopathy may occur, usually resolving after discontinuation of the drug. Extrapyramidal tremor, cerebellar ataxia, and rarely, benign intracranial hypertension (pseudotumor of the brain), nightmares may be observed. Nausea, vomiting, and dyspepsia are possible, which are usually noted when using a saturating dose and their severity decreases when the dose is reduced. Alopecia is possible. In some cases, epididymitis may occur, and rarely, impotence. The connection between these side effects and treatment with Cordarone has not been established. Rarely, hypersensitivity reactions such as vasculitis, kidney damage with increased creatinine levels, and thrombocytopenia may occur. Hemolytic or aplastic anemia can occur extremely rarely. With intravenous administration, a decrease in blood pressure may develop (usually moderate and reversible); with an overdose and too rapid administration, severe hypotension or collapse, a feeling of heat, sweating, and nausea may develop. Arrhythmia may develop or intensify.

Cordarone 50mg/ml 3ml 6 pcs. solution for intravenous administration

pharmachologic effect

Antiarrhythmic.

Composition and release form Cordarone 50 mg/ml 3 ml 6 pcs. solution for intravenous administration

Dividable tablets - 1 tablet:

• amiodarone hydrochloride - 200 mg;
• excipients: lactose monohydrate; corn starch; magnesium stearate; povidone K90F; anhydrous colloidal silicon dioxide.

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.

Tablets, 200 mg. There are 10 pcs in a blister; There are 3 blisters in a cardboard pack.

Solution for intravenous administration. In ampoules of 3 ml; in a box 6 pcs.

Description of the dosage form

Tablets: round, white to off-white in color, with a break line on one side and beveled on both sides. There is an engraving: a heart symbol above the fault line and 200 below the fault line and a bevel from the edges to the fault line.

Solution: transparent solution of light yellow color.

Directions for use and doses

Pills.

Inside, before meals, with plenty of water. The drug should be taken only as prescribed by a doctor!

Loading (“saturating”) dose: various saturation schemes can be used.

In hospital: the initial dose, divided into several doses, ranges from 600–800 mg (up to a maximum of 1200 mg) per day until a total dose of 10 g is reached (usually over 5–8 days).

Outpatient: the initial dose, divided into several doses, is from 600 to 800 mg per day until a total dose of 10 g is reached (usually over 10-14 days).

Maintenance dose: may vary in different patients from 100 to 400 mg/day. The minimum effective dose should be used according to the individual therapeutic outcome.

Since Cordarone has a very long half-life, it can be taken every other day or take breaks 2 days a week.

The average therapeutic single dose is 200 mg. The average therapeutic daily dose is 400 mg. The maximum single dose is 400 mg. The maximum daily dose is 1200 mg.

Injection.

IV administration: Cordarone (injection form) is intended for use in cases where rapid achievement of an antiarrhythmic effect is required, or if oral administration of the drug is not possible.

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

When administered intravenously, Cordarone should not be mixed with other drugs. Other drugs should not be administered into the same infusion line as Cordarone. Use only in diluted form. To dilute the drug Cordarone, you should use only a 5% dextrose (glucose) solution. Due to the characteristics of the dosage form of the drug, it is not recommended to use concentrations of the infusion solution less than those obtained by diluting 2 ampoules in 500 ml of 5% dextrose (glucose).

To avoid injection site reactions, amiodarone should be administered through a central venous catheter, except in cases of cardiac resuscitation for ventricular fibrillation refractory to cardioversion, when, in the absence of central venous access, peripheral veins (the largest peripheral vein with maximum blood flow) can be used to administer the drug ).

Severe cardiac arrhythmias, in cases where it is impossible to take the drug orally (except in cases of cardiac resuscitation for cardiac arrest caused by ventricular fibrillation, resistant to cardioversion).

Intravenous drip through a central venous catheter

Typically the loading dose is 5 mg/kg in 250 ml of 5% dextrose (glucose) solution, administered using an electronic pump whenever possible over 20–120 minutes. It can be administered repeatedly 2-3 times within 24 hours. The rate of administration of the drug is adjusted depending on the clinical effect. The therapeutic effect appears within the first minutes of administration and gradually decreases after stopping the infusion, therefore, if it is necessary to continue treatment with injectable Cordarone, it is recommended to switch to constant intravenous drip administration of the drug.

Maintenance doses: 10–20 mg/kg/day (usually 600–800 mg, but can be increased to 1200 mg/day) in 250 ml of 5% dextrose (glucose) solution for several days. From the first day of infusion, a gradual transition to taking Cordarone orally should begin (3 tablets, 200 mg per day). The dose can be increased to 4 or even 5 tablets. 200 mg per day.

Cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to cardioversion

Intravenous bolus administration

The first dose is 300 mg (or 5 mg/kg) of cordarone, diluted in 20 ml of a 5% dextrose (glucose) solution and administered intravenously (boost).

If fibrillation does not stop, then additional intravenous jet administration of Cordarone at a dose of 150 mg (or 2.5 mg/kg) is possible.

Pharmacodynamics

Amiodarone belongs to class III antiarrhythmic drugs (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-blocker effect.

In addition to the antiarrhythmic effect, it has antianginal, coronary dilation, alpha and beta adrenergic blocking 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 a class III antiarrhythmic according to the Vaughan-Williams classification);
• a decrease in the automaticity of the sinus node, leading to a decrease in 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 conductivity;
• 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 down conduction and increasing the duration of the refractory period in additional atrioventricular conduction bundles.

Other effects:

• absence of 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 the beta-adrenergic blocking effect;
• an increase in coronary blood flow due to a direct effect on the smooth muscle of the coronary arteries;
• maintaining cardiac output by reducing aortic pressure and reducing peripheral resistance;
• influence on the exchange of thyroid hormones: inhibition of the conversion of T3 to T4 (blockade of thyroxine-5-deiodinase) 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 a week after starting to take the drug (from several days to two weeks). After stopping its use, amiodarone is detected in the blood plasma for 9 months. The possibility of maintaining the pharmacodynamic effect of amiodarone for 10–30 days after its discontinuation should be taken into account.

Pharmacokinetics

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 blood plasma is achieved within 3–7 hours. However, the therapeutic effect usually develops a week after starting the drug (from several days to 2 weeks). Amiodarone is a drug with a slow release into tissues and high affinity for them.

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, in the liver, lungs, spleen and cornea.

Amiodarone is metabolized in the liver via isoenzymes CYP3A4 and CYP2C8. Its main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. Amiodarone and its active metabolite desethylamiodarone in vitro have the ability to inhibit the isoenzymes CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and desethylamiodarone have also demonstrated the ability to inhibit certain transporters, such as P-glycoprotein (P-gp) and organic cation transporter (POK2). In vivo, interactions of amiodarone with substrates of the isoenzymes CYP3A4, CYP2C9, CYP2D6 and P-gp were observed.

The elimination of amiodarone begins within a few days, and achieving equilibrium between the intake and elimination of the drug (achieving an equilibrium state) occurs after one to several months, depending on the individual characteristics of the patient. The main route of elimination of amiodarone is the intestine. Amiodarone and its metabolites are not eliminated 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 when taken orally occurs in 2 phases: initial T1/2 (first phase) - 4-21 hours, T1/2 in the 2nd phase - 25-110 days (20-100 days). After prolonged oral administration, the average T1/2 is 40 days. After discontinuation of the drug, complete elimination of amiodarone from the body may continue 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 with 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 amiodarone concentrations.

The pharmacokinetics of the drug explain the use of “loading” doses, which are aimed at quickly achieving the required level of tissue saturation at which its therapeutic effect is manifested.

Pharmacokinetics in renal failure: due to the insignificant excretion of the drug by the kidneys in patients with renal failure, no dose adjustment of amiodarone is required.

With intravenous administration of Cordarone, its activity reaches a maximum after 15 minutes and disappears approximately 4 hours after administration. After administration of amiodarone, its concentration in the blood decreases rapidly due to the drug entering the tissues. In the absence of repeated injections, the drug is gradually eliminated. When resuming its intravenous administration or when prescribing the drug orally, amiodarone accumulates in the tissues. Amiodarone has a large volume of distribution and can accumulate in almost all tissues, especially in adipose tissue and in addition to it in the liver, lungs, spleen and cornea

Amiodarone and its metabolites are not dialyzable.

It is mainly excreted with bile and feces through the intestines. Amiodarone elimination is very slow. Amiodarone and its metabolites are detected in blood plasma for 9 months after cessation of treatment.

Indications for use Cordarone 50 mg/ml 3 ml 6 pcs. solution for intravenous administration

Pills

Relapse prevention:

• life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be started in the 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 reduced left ventricular ejection fraction (less than 40%).
• treatment of rhythm disturbances in patients with coronary artery disease and/or left ventricular dysfunction.

Injectable form of Cordarone

• 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;
• Cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to defibrillation.

Contraindications

Common to both dosage forms

• hypersensitivity to iodine, amiodarone or excipients of the drug;
• sick sinus syndrome (sinus bradycardia, sinoatrial block), except in cases of correction of the sinus node with an artificial driver).
• AV blockade of II–III degree, two- and three-fascicle blockades 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 ventricular torsade de pointes:
• 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 neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular erythromycin when administered intravenously, spiramycin); azoles; antimalarials (quinine, chloroquine, mefloquine, halofantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones.

For tablets additionally: interstitial lung disease.

For the injection form additionally:

• violations of intraventricular conduction (two- and three-fascicle blockades) in the absence of a permanent artificial pacemaker (pacemaker) - in these cases, IV amiodarone can be used in specialized departments under the cover of an artificial pacemaker (pacemaker);
• severe arterial hypotension, collapse, cardiogenic shock;
• IV jet administration is contraindicated in the case of arterial hypotension, severe respiratory failure, cardiomyopathy or heart failure (these conditions may be aggravated).

All of the above contraindications do not apply to the use of Cordarone during cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to cardioversion.

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

Application Cordarone 50 mg/ml 3 ml 6 pcs. solution for intravenous administration during pregnancy and lactation

Pregnancy

Currently available clinical information is insufficient to determine the possibility or impossibility of developmental defects in the embryo when amiodarone is used in the first trimester of pregnancy.

Since the fetal thyroid gland begins to bind iodine only from the 14th week of pregnancy, it is not expected to be affected by amiodarone if it is used earlier. Excess iodine when using the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in the newborn or even to the formation of a clinically significant goiter.

Due to the effect of the drug on the fetal thyroid gland, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit outweighs the risk (in case of life-threatening ventricular arrhythmias).

Lactation period

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

Overdose

Symptoms: With oral administration of very large doses, several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal tachycardia of the “pirouette” type and liver damage have been described. Possible slowdown of atrioventricular conduction, worsening of existing heart failure.

Treatment: symptomatic (gastric lavage, administration of activated charcoal (if the drug has been taken recently), in other cases symptomatic therapy is carried out: for bradycardia - beta-adrenergic stimulants or installation of a pacemaker, for tachycardia of the "pirouette" type - intravenous administration of magnesium salts or cardiac stimulation. Neither amiodarone nor its metabolites are removed by hemodialysis and there is no specific antidote.

There is no information on overdose of amiodarone for intravenous administration.

Side effects Cordarone 50 mg/ml 3 ml 6 pcs. solution for intravenous administration

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

Pills.

From the cardiovascular system: often - moderate bradycardia, the severity of which depends on the dose of the drug. Uncommon: conduction disturbances (sinoatrial block, AV block of various degrees); arrhythmogenic effect (there are reports of the emergence of new arrhythmias or aggravation of existing ones, in some cases with subsequent cardiac arrest). In light of the available data, it is impossible to determine whether this is a consequence of the drug, or related to the severity of cardiac damage, or a consequence of treatment failure. These effects are observed mainly when Cordarone is used in conjunction with drugs that prolong the period of repolarization of the ventricles of the heart (QTc interval) or in cases of electrolyte imbalance. Very rarely - severe bradycardia or, in exceptional cases, sinus node arrest, which were observed in some patients (patients with sinus node dysfunction and elderly patients). Frequency unknown - progression of chronic heart failure (with long-term use).

From the digestive system: very often - nausea, vomiting, loss of appetite, dullness or loss of taste, feeling of heaviness in the epigastrium, especially at the beginning of treatment; passing after dose reduction; isolated increase in transaminase activity in the blood serum, usually moderate (1.5-3 times higher than normal values) and decreasing with decreasing dose or even spontaneously. Often - acute liver damage with increased transaminases and/or jaundice, including the development of liver failure, sometimes fatal. Very rarely - chronic liver diseases (pseudoalcoholic hepatitis, cirrhosis) are sometimes fatal. Even with a moderate increase in transaminase activity in the blood, observed after treatment lasting more than 6 months, chronic liver damage should be suspected.

From the respiratory system: often - cases of interstitial or alveolar pneumonitis and bronchiolitis obliterans with pneumonia have been reported, sometimes resulting in death. Several cases of pleurisy have been reported. These changes may lead to the development of pulmonary fibrosis, but they are largely reversible with early discontinuation of amiodarone, with or without corticosteroids. Clinical manifestations usually disappear within 3–4 weeks. Recovery of the X-ray picture and lung function occurs more slowly (several months). The appearance of severe shortness of breath or a dry cough in a patient receiving amiodarone, either accompanied or not accompanied by a deterioration in general condition (increased fatigue, loss of body weight, increased body temperature), requires a chest x-ray and, if necessary, discontinuation of the drug. Very rarely - bronchospasm in patients with severe respiratory failure, especially in patients with bronchial asthma; acute respiratory distress syndrome, sometimes fatal and sometimes immediately after surgery (possible interaction with high doses of oxygen). Frequency not known: pulmonary hemorrhage.

From the senses: very often - microdeposits in the corneal epithelium, consisting of complex lipids, including lipofuscin, they are usually limited to the pupil area and do not require cessation of treatment and disappear after discontinuation of the drug. Sometimes they can cause visual disturbances in the form of a colored halo or blurred contours in bright light. Very rare - a few cases of optic neuritis/optic neuropathy have been described. Their connection with amiodarone has not yet been established. However, since optic neuritis can lead to blindness, if blurred vision or decreased visual acuity occurs while taking Cordarone, it is recommended to perform a full ophthalmological examination, including fundoscopy, and if optic neuritis is detected, discontinue amiodarone.

Endocrine disorders: often - hypothyroidism with its classic manifestations: weight gain, chilliness, apathy, decreased activity, drowsiness, bradycardia that is excessive compared to the expected effect of amiodarone. The diagnosis is confirmed by identifying an elevated serum TSH level. Normalization of thyroid function is usually observed within 1–3 months after cessation of treatment. In life-threatening situations, treatment with amiodarone can be continued, with simultaneous additional administration of L-thyroxine under monitoring of serum TSH levels. Hyperthyroidism, the appearance of which is possible during and after treatment (cases of hyperthyroidism that developed several months after discontinuation of amiodarone have been described). Hyperthyroidism occurs more silently with a small number of symptoms: minor unexplained weight loss, decreased antiarrhythmic and/or antianginal effectiveness; mental disorders in elderly patients or even the phenomenon of thyrotoxicosis. The diagnosis is confirmed by identifying a reduced serum TSH level (an ultrasensitive criterion). If hyperthyroidism is detected, amiodarone should be discontinued. Normalization of thyroid function usually occurs within several months after discontinuation of the drug. In this case, clinical symptoms normalize earlier (after 3–4 weeks) than normalization of thyroid hormone levels occurs. Severe cases can be fatal, so urgent medical intervention is required in such cases. Treatment in each individual case is selected individually. If the patient's condition worsens, both due to thyrotoxicosis itself and due to a dangerous imbalance between myocardial oxygen demand and its delivery, it is recommended to immediately begin treatment with corticosteroids (1 mg/kg), continuing it for a long time (3 months), instead the use of synthetic antithyroid drugs, which may not always be effective in this case. Very rarely - syndrome of impaired secretion of antidiuretic hormone.

From the skin: very often - photosensitivity. Often - in case of prolonged use of the drug in high daily doses, grayish or bluish pigmentation of the skin may be observed; After stopping treatment, this pigmentation slowly disappears. Very rarely - during radiation therapy, cases of erythema may occur, there are reports of skin rash, usually of little specificity, isolated cases of exfoliative dermatitis (no connection with the drug has been established); alopecia.

From the central nervous system: often - tremor or other extrapyramidal symptoms; sleep disorders, incl. nightmares. Rarely - sensorimotor, motor and mixed peripheral neuropathies and/or myopathy, usually reversible after discontinuation of the drug. Very rarely - cerebellar ataxia, benign intracranial hypertension (pseudotumor cerebri), headache.

Other: very rarely - vasculitis, epididymitis, several cases of impotence (no connection with the drug has been established), thrombocytopenia, hemolytic anemia, aplastic anemia.

Injection

From the cardiovascular system: often - bradycardia (usually a moderate decrease in heart rate); decrease in blood pressure, usually moderate and transient. Cases of severe arterial hypotension or collapse have been observed with overdose or too rapid administration of the drug. Very rarely - proarrhythmogenic effect (there are reports of the occurrence of new arrhythmias, including polymorphic ventricular tachycardia of the “pirouette” type, or aggravation of existing ones - in some cases with subsequent cardiac arrest). These effects are observed mainly in cases where Cordarone is used in conjunction with drugs that prolong the period of repolarization of the ventricles of the heart (QTc interval) or in case of electrolyte imbalance (see “Interaction”). In light of the available data, it is impossible to determine whether the occurrence of these rhythm disturbances is caused by Cordarone, or is associated with the severity of cardiac pathology, or is a consequence of treatment failure. Severe bradycardia or, in exceptional cases, sinus node arrest, which were observed in some patients (patients with sinus node dysfunction and elderly patients), flushing of the facial skin, progression of heart failure (possibly with intravenous jet administration).

From the respiratory system: very rarely - cough, shortness of breath, interstitial pneumonitis; bronchospasm and/or apnea in patients with severe respiratory failure, especially in patients with bronchial asthma; acute respiratory distress syndrome, sometimes fatal and sometimes immediately after surgery (possible interaction with high oxygen concentrations).

From the digestive system: very often - nausea. Very rarely - an isolated increase in the activity of hepatic transaminases in the blood serum, usually moderate (1.5-3 times higher than normal values) and decreasing with decreasing dose or even spontaneously. Acute liver damage (within 24 hours after administration of amiodarone) with increased transaminases and/or jaundice, including the development of liver failure, sometimes fatal.

From the skin: very rarely - feeling of heat, increased sweating.

From the side of the central nervous system: very rarely - benign intracranial hypertension (pseudotumor cerebri), headache.

Immune system disorders: very rarely - anaphylactic shock. Unknown frequency: angioedema.

Reactions at the injection site: often - inflammatory reactions, such as superficial phlebitis, when administered directly into a peripheral vein. Reactions at the injection site, such as: pain, erythema, swelling, necrosis, extravasation, infiltration, inflammation, induration, thrombophlebitis, phlebitis, cellulitis, infection, pigmentation.

Drug interactions

Drugs that can cause torsade de pointes or prolong the QT interval

Drugs that can cause ventricular torsade de pointes. Combination therapy with drugs that can cause torsade de pointes is contraindicated, as the risk of developing potentially fatal torsade de pointes increases.

Antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide, procainamide), sotalol, bepridil.

Other (non-antiarrhythmic) drugs: vincamine; some neuroleptics - phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole; terfenadine

Drugs that can prolong the QT interval. Co-administration of amiodarone with drugs that can prolong the QT interval should be based on a careful assessment for each patient of the relationship between the expected benefit and the potential risk (the possibility of an increased risk of developing torsade de pointes). When using such combinations, constant monitoring of the ECG (to detect prolongation of the QT interval), potassium and magnesium levels in the blood is necessary.

Fluoroquinolones, including moxifloxacin, should be avoided in patients taking amiodarone.

Drugs that reduce heart rate or cause automaticity or conduction disorders

Combination therapy with these drugs is not recommended.

Beta-blockers, CCBs that reduce heart rate (verapamil, diltiazem) can cause disturbances in automaticity (development of excessive bradycardia) and conduction.

Drugs that can cause hypokalemia

Not recommended combinations. With laxatives that stimulate intestinal motility and can cause hypokalemia, which increases the risk of developing ventricular “pirouette” tachycardia. When combined with amiodarone, laxatives from other groups should be used.

Combinations that require caution when used. With diuretics that cause hypokalemia (in monotherapy or combinations with other drugs); systemic corticosteroids (GCS, mineralocorticosteroids), tetracosactide; amphotericin B (iv administration).

It is necessary to prevent the development of hypoglycemia, and if it occurs, restore the potassium content in the blood to normal levels, monitor the concentration of electrolytes in the blood and ECG (for possible prolongation of the QT interval); in the event of ventricular “pirouette” tachycardia, antiarrhythmic drugs should not be used (should Ventricular pacing should be started; intravenous administration of magnesium salts is possible).

Preparations for inhalation anesthesia

The possibility of developing the following severe complications in patients receiving amiodarone while receiving general anesthesia has been reported: bradycardia (resistant to atropine), arterial hypotension, conduction disturbances, and decreased cardiac output.

Very rare cases of severe complications from the respiratory system, sometimes fatal, have been observed - acute respiratory distress syndrome in adults, which developed immediately after surgery, the occurrence of which is associated with high oxygen concentrations.

Drugs that slow heart rate

Clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine - risk of developing excessive bradycardia (cumulative effects).

Special instructions for use

During treatment with Cordarone, ECG changes are possible - prolongation of the Q-T (due to prolonged repolarization), the appearance of a U . These changes are not a manifestation of toxicity. In elderly patients, heart rate may decrease more pronouncedly. The drug should be discontinued if II-III degree AV block, sinoatrial block or Hiss bundle block occurs. Cases of dyspnea or nonproductive cough may be a manifestation of pulmonary toxicity of the drug . Cordarone contains iodine and may therefore interfere with the absorption of radioactive iodine. Cordarone may cause thyroid dysfunction (see SIDE EFFECTS), especially in patients with thyroid dysfunction (including a family history). Therefore, careful clinical and laboratory monitoring should be carried out before the start of treatment, during treatment and several months after the end of treatment. If thyroid dysfunction is suspected, the level of thyroid-stimulating hormone in the blood serum should be determined. During treatment, regular liver function tests (transaminase activity) are recommended. Before starting treatment with Cordarone, it is recommended to conduct an ECG study, determination of thyroid-stimulating hormone and potassium levels in the blood serum. Side effects of the drug are usually dose-related; therefore, caution should be used when determining the minimum effective maintenance dose. Patients should be warned to avoid exposure to insolation and ultraviolet radiation during treatment. The safety and effectiveness of amiodarone in children have not been studied. Before an operation requiring anesthesia, the anesthesiologist should be informed that the patient is taking amiodarone. There is no data on the effect of Cordarone on the ability to drive vehicles and perform work requiring increased attention. Due to the effect of the drug on the fetal thyroid gland, the use of Cordarone is contraindicated during pregnancy, except in special cases. Amiodarone is excreted in breast milk in significant quantities, so it is contraindicated during breastfeeding.

Drug interactions Cordarone

The simultaneous use of Cordarone with drugs that can cause paroxysmal ventricular tachycardia of the torsade de pointes type is contraindicated:

• class Ia antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
• class III antiarrhythmic drugs (sotalol, dofetilide, ibutilide);
• bepridil, cisapride, difemanil, erythromycin for intravenous administration, mizolastine, sparfloxacin, vincamine for intravenous administration;
• sultopride.

There is an increased risk of developing ventricular arrhythmias, especially paroxysmal tachycardia of the torsade de pointes type, when used simultaneously with sparfloxacin due to prolongation of the QT on the ECG (additive electrophysiological effect). Combination therapy with the following drugs is not recommended:

• neuroleptics that can cause paroxysmal tachycardia of the torsade de pointes type, some phenothiazine neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), pimozide (increased risk of developing ventricular aritis miy, especially paroxysmal tachycardia such as torsade de pointes);
• halofantrine, moxifloxacin, pentamidine (increased risk of developing ventricular arrhythmias, especially paroxysmal tachycardia of the torsade de pointes type. If such a combination is unavoidable, preliminary monitoring of the QT and constant ECG monitoring in the future are necessary);
• injectable form of diltiazem (risk of developing bradycardia and AV block. If such a combination is necessary, careful monitoring of the patient's condition and constant ECG monitoring are required);
• β-adrenergic receptor blockers, except sotalol and esmolol (risk of impaired automaticity, conduction and contractility of the heart due to suppression of sympathetic compensatory mechanisms).

The following drugs should be prescribed with caution in combination with Cordarone: Oral anticoagulants. Due to the increased effect of oral anticoagulants and the increased risk of bleeding, it is necessary to more often monitor the level of prothrombin in the blood and adjust the dose of oral anticoagulants during treatment with Cordarone and after discontinuation of the drug. Cyclosporine. There may be an increase in the level of cyclosporine in the blood plasma, associated with a decrease in its metabolism in the liver, which increases the nephrotoxicity of the drug. In this case, dose adjustment is necessary. Oral forms of diltiazem. Risk of developing bradycardia and AV block, especially in elderly patients. Clinical and ECG monitoring is required. Foxglove preparations . There may be a violation of automaticity (severe bradycardia) and AV conduction. It is possible to increase the concentration of digoxin in the blood plasma (due to a decrease in its clearance). It is necessary to carry out ECG studies, clinical and biochemical monitoring (including, if necessary, determination of the level of digoxin in the blood plasma); It may be necessary to change the dose of cardiac glycosides. Esmolol. There may be a violation of the automaticity, conductivity and contractility of the heart (suppression of sympathetic compensatory mechanisms). Clinical and cardiographic monitoring of the patient's condition is necessary. Drugs that can cause hypokalemia:

• diuretics that cause hypokalemia on their own or in combination with other drugs;
• stimulant laxatives;
• systemic corticosteroids (gluco-, mineralo-), tetracosactide;
• amphotericin B (iv use).

Increased risk of developing ventricular arrhythmias, especially paroxysmal tachycardia such as torsade de pointes (hypokalemia is a predisposing factor). Clinical and cardiographic monitoring of the patient’s condition and monitoring of serum potassium levels are recommended. Phenytoin. It is possible to increase the level of phenytoin in the blood plasma with symptoms of overdose (in particular of a neurological nature). Clinical monitoring and dose reduction of phenytoin is necessary if signs of overdose occur; if possible, determine the level of phenytoin in the blood plasma. Drugs that cause bradycardia. Calcium channel blockers (diltiazem, verapamil), β-adrenergic receptor blockers (except sotalol), clonidine, guanfacine, digitalis preparations, mefloquine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambemonium, pyridostigmine, neostigmine). Increased risk of developing ventricular arrhythmias, especially paroxysmal tachycardia such as torsade de pointes. Clinical and ECG monitoring is recommended. Simvastatin. Dose-dependent increase in the risk of side effects such as rhabdomyolysis (decreased metabolism of simvastatin in the liver). The dose of simvastatin should not exceed 20 mg per day. If a therapeutic effect cannot be achieved when used at such a dose, it is necessary to prescribe another statin that does not interact with Cordarone. Anesthetic agents. Potentially serious complications may occur in patients undergoing general anesthesia: bradycardia not corrected by atropine, hypotension, conduction disturbances, decreased cardiac output. Very rarely - severe respiratory complications, sometimes resulting in death (acute adult respiratory distress syndrome). Typically, they are observed immediately after surgery, possibly due to incompatibility with high oxygen concentrations.

Overdose of the drug Cordarone, symptoms and treatment

Information regarding overdose of Cordarone is limited. In some cases, sinus bradycardia, ventricular arrhythmia, torsade de pointes tachycardia, liver damage, and vascular insufficiency were observed. Considering the pharmacokinetic profile of the drug, it is recommended to monitor the patient’s condition over a long period of time (especially monitoring of cardiac activity). Treatment is symptomatic. Neither Cordarone nor its metabolites are removed by dialysis.