Cordarone tablets 200 mg 30 pcs.

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.

Disorders of the blood and lymphatic system. Very rare: – Hemolytic anemia, aplastic anemia, thrombocytopenia. Frequency unknown: – Neutropenia, agranulocytosis. Cardiac disorders. Common: – Bradycardia, usually moderate and dose-dependent. Uncommon: – Arrhythmogenic effect (the emergence of new rhythm disturbances or worsening of existing rhythm disturbances, in some cases with subsequent cardiac arrest). Very rare: – Severe bradycardia or sinus arrest in patients with sinus node dysfunction and/or elderly patients. Frequency unknown: – Conduction disorders (sinoatrial block, atrioventricular block of varying degrees of severity). – Ventricular “pirouette” tachycardia. Endocrine system disorders. Common: – Hypothyroidism. – Hyperthyroidism, sometimes fatal. Very rare: – Syndrome of impaired secretion of antidiuretic hormone. Violations of the organ of vision. Very common: – Microdeposits in the corneal epithelium, consisting of complex lipids. They are usually limited to the pupil area and disappear after discontinuation of the drug. Sometimes they can cause visual disturbances such as the appearance of a colored halo in bright light or blurred vision. Very rare: – Neuropathy/optic neuritis, which may progress to blindness. Disorders of the digestive system. Very common: – Nausea, vomiting, dysgeusia (dullness or loss of taste), usually occurring when taking a loading dose and resolving after dose reduction. Frequency unknown: – Pancreatitis/acute pancreatitis, dry mouth, constipation. General disorders. Not known: – Granuloma formation, including bone marrow granuloma. Disorders of the liver and biliary tract. Very common: – An isolated increase in serum transaminase activity, usually moderate (1.5 to 3 times the upper limit of normal), observed at the beginning of treatment. The activity of “liver” transaminases may return to normal values when the dose is reduced or even spontaneously. Common: – Acute liver damage with increased transaminase activity and/or jaundice, including the development of liver failure, sometimes with death. Very rare: – Chronic liver diseases (pseudoalcoholic hepatitis, cirrhosis), sometimes fatal. Immune system disorders. Frequency unknown: – Angioedema (Angioedema), anaphylactic/anaphylactoid reactions, including shock. Laboratory and instrumental data. Very rare: – Increased serum creatinine concentration. Metabolic and nutritional disorders. Frequency unknown: – Decreased appetite. Nervous system disorders. Common: – Extrapyramidal tremor, nightmares, sleep disturbances. Uncommon: – Peripheral sensorimotor neuropathy and/or myopathy, usually reversible after discontinuation of the drug. Very rare: – Cerebellar ataxia, benign intracranial hypertension (pseudotumor cerebri), headache. Frequency unknown: – Parkinsonism, parosmia (disorder of the sense of smell, especially the subjective perception of an objectively absent smell). Mental disorders. Frequency unknown: – Confusion/delirium, hallucinations. Disorders of the genital organs and mammary gland. Very rarely: – Epididymitis, impotence. Frequency unknown: – Decreased libido. Disorders of the respiratory system, chest and mediastinal organs. Common: – Pulmonary toxicity (alveolar/interstitial pneumonitis or fibrosis, pleurisy, bronchiolitis obliterans with organizing pneumonia [cryptogenic organizing pneumonia]), sometimes fatal. Very rare: – Bronchospasm in patients with severe respiratory failure, especially in patients with bronchial asthma. – Acute adult respiratory distress syndrome, sometimes fatal, usually occurring immediately after surgery (possible interaction with high oxygen concentrations). Frequency unknown: – Pulmonary hemorrhage. Disorders of the skin and subcutaneous tissues. Very common: – 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; skin rash, usually nonspecific, exfoliative dermatitis, alopecia. Not known: – Eczema, urticaria, severe skin reactions, sometimes fatal, including toxic epidermal necrolysis/Stevens-Johnson syndrome, bullous dermatitis; drug reaction with eosinophilia and systemic symptoms. Vascular disorders. Very rare: – Vasculitis.

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.

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.

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®

Amiodarone may cause severe adverse reactions in the heart, thyroid, eyes, lungs, liver, skin, and peripheral nervous system. Since these adverse reactions may be delayed, patients taking Cordarone® for a long time should be closely monitored throughout the entire period of treatment, as well as for several months after its cessation.

Side effects of the drug Cordarone® are usually dose-dependent, therefore, to minimize the possibility of their occurrence, the minimum effective dose should be used.

Heart disorders

Before starting to take the drug Cordarone®, it is recommended to conduct an electrocardiographic study (ECG) and determine the potassium content in the blood serum. Hypokalemia must be corrected before using Cordarone®.

The pharmacological effect of the drug Cordarone® causes ECG changes: prolongation of the QT interval, QTC (corrected), associated with an extension of the period of repolarization of the ventricles of the heart, with the possible appearance of U waves. However, these changes are not a manifestation of the toxic effect of the drug Cordarone®. It is permissible to increase the QTC interval by no more than 450 ms or by no more than 25% of the original value.

The use of amiodarone in high doses can lead to the development of severe bradycardia and cardiac conduction disturbances with the appearance of idioventricular heart rhythm, especially in elderly patients and with simultaneous use of cardiac glycosides. In such cases, the use of the drug should be discontinued. If necessary, beta-agonists or glucagon can be prescribed. Given the long half-life of amiodarone, the possibility of installing a temporary pacemaker should be considered.

Amiodarone can be used in patients with latent or manifest chronic heart failure. In this case, the drug should be used with caution in decompensated or severe chronic heart failure (III-IV functional class according to the NYHA classification), because Amiodarone in some cases can lead to its worsening.

Elderly patients are at increased risk of developing severe bradycardia when using amiodarone.

If first degree atrioventricular block occurs, monitoring of the patient's condition should be intensified. In the event of the development of atrioventricular block II and III degrees, sinoatrial block or two-beam/three-beam intraventricular block, treatment with Cordarone® should be discontinued.

The occurrence of new rhythm disturbances or worsening of existing rhythm disturbances, sometimes with fatal outcome, has been reported. It is very important, although difficult, to make a differential diagnosis between the insufficient antiarrhythmic effectiveness of the drug and its arrhythmogenic effect (regardless of whether it is combined or not with aggravation of the severity of heart disease).

When using the drug Cordarone®, arrhythmogenic effects were reported much less frequently than when using other antiarrhythmic drugs. It has generally been observed in the presence of factors that prolong the QT interval, such as interactions with other drugs and/or blood electrolyte disturbances. Despite its ability to prolong the QT interval, amiodarone has a low potential for torsade de pointes (TdP).

Patients with a pacemaker/implanted cardioverter-defibrillator

Increased frequency of ventricular defibrillation and/or increased threshold for pacemaker or implantable cardioverter defibrillator (ICD) response has been reported in patients receiving long-term antiarrhythmic drugs. Amiodarone may increase the pacing threshold in patients with a pacemaker and the defibrillation threshold in patients with an ICD. In this regard, to ensure adequate functioning of these implantable devices in patients receiving therapy with Cordarone®, it is recommended to regularly monitor pacing/defibrillation parameters.

Severe bradycardia with simultaneous use of amiodarone with antiviral drugs

When Cordarone® was used in combination with sofosbuvir in monotherapy or in combination with other direct-acting antiviral drugs against viral hepatitis C, such as daclatasvir, simeprevir, ledipasvir, cases of severe, potentially life-threatening bradycardia, as well as heart block, were observed. Therefore, the simultaneous use of these drugs with Cordarone® is not recommended.

If concomitant use of these drugs with Cordarone® cannot be avoided, careful monitoring of patients is recommended after starting sofosbuvir in combination with other direct-acting antivirals. After concomitant use of sofosbuvir is initiated, patients who are at high risk of developing bradyarrhythmias should be monitored continuously in a hospital setting for at least 48 hours.

Due to the long half-life of amiodarone, appropriate monitoring should also be performed in patients who have stopped taking Cordarone® within the last few months before starting treatment with sofosbuvir alone or in combination with other direct-acting antivirals.

Patients taking the above medicinal products against hepatitis C virus in combination with Cordarone®, either in combination with other medicinal products that slow the heart rate or without combination with such medicinal products, should be informed about symptoms indicating the development of bradycardia and heart block. hearts. If they occur, they should seek medical attention immediately.

Thyroid disorders

Amiodarone can cause the development of both hypothyroidism (decreased thyroid function) and hyperthyroidism (increased thyroid function), especially in patients with a history of thyroid disease.

Because amiodarone contains iodine, its use may interfere with the absorption of radioactive iodine and distort the results of radioisotope studies of the thyroid gland. However, taking the drug does not affect the reliability of determining the concentration of free triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) (using an ultrasensitive assay) in the blood serum.

Before using amiodarone, all patients should undergo a clinical and laboratory examination (determining the concentration of TSH in the blood serum using an ultrasensitive assay) to identify abnormal thyroid function.

The patient should be monitored regularly (at 6-month intervals) during treatment with amiodarone and for several months after its cessation in order to identify clinical or laboratory signs of changes in thyroid function. Particularly careful monitoring is necessary when using the drug in elderly patients and in patients with a history of thyroid disease. If thyroid dysfunction is suspected, it is necessary to determine the concentration of TSH in the blood serum (using an ultrasensitive test).

Amiodarone inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increased serum free T4 concentrations with slightly decreased or even normal serum free T3 concentrations) in clinically euthyroid patients, which is not the cause to discontinue the drug Cordarone®.

Hypothyroidism

The development of hypothyroidism can be suspected when the following clinical signs appear: weight gain, cold intolerance, decreased activity, severe bradycardia. The diagnosis is confirmed by an increase in the concentration of TSH in the blood serum, determined using an ultrasensitive analysis. Normalization of thyroid function is usually observed within 1-3 months after cessation of treatment.

In life-threatening situations (for example, when using the drug for the prevention of life-threatening ventricular arrhythmias), treatment with Cordarone® can be continued with simultaneous additional use of levothyroxine drugs under the control of serum TSH concentrations.

Hyperthyroidism

While taking Cordarone® or for several months after stopping it, hyperthyroidism may develop. Particular attention should be paid to symptoms such as weight loss, asthenia, anxiety, emotional lability, rapid heartbeat, the occurrence or increase in rhythm disturbances and/or angina attacks, the occurrence or worsening of chronic heart failure. The diagnosis is confirmed by identifying a decrease in the concentration of TSH in the blood serum, determined using an ultrasensitive analysis. In this case, taking Cordarone® should be discontinued. Recovery usually occurs within several months after treatment is stopped; First, the disappearance of clinical manifestations is observed, and then normalization of laboratory parameters of thyroid function occurs. Severe cases of amiodarone-induced thyrotoxicosis, which can sometimes be fatal (both due to the thyrotoxicosis itself and due to a dangerous imbalance between myocardial oxygen demand and oxygen supply), require urgent treatment. Treatment should be selected individually in each specific case: antithyroid drugs (which may not always be effective), glucocorticosteroids, beta-blockers.

Visual disorders

Amiodarone may cause the development of neuropathy/optic neuritis. If blurred vision occurs or visual acuity decreases, it is necessary to urgently conduct a complete ophthalmological examination, including examination of the fundus (funduscopy). If neuropathy and/or optic neuritis is detected, Cordarone® should be discontinued due to the risk of their progression up to the development of blindness. Regardless of the presence or absence of visual impairment, with long-term use of the drug Cordarone®, an annual ophthalmological examination is recommended.

Lung disorders

Lung lesions (interstitial/alveolar pneumonitis or fibrosis, pleurisy, bronchiolitis obliterans with organizing pneumonitis), sometimes fatal, have been reported with the use of amiodarone. Manifestations of pulmonary toxicity include shortness of breath (which may be severe and not consistent with the severity of damage to the cardiovascular system), non-productive dry cough and deterioration of general condition (increased fatigue, weight loss, fever). Symptoms are usually mild at first but progress quickly. In most cases, lung lesions develop with long-term use of amiodarone, but in some cases they can occur a short time (from several days to several weeks) after the start of treatment.

A thorough clinical evaluation is recommended before use of amiodarone in all patients; In some cases, it is advisable to perform a chest x-ray. If the development of interstitial pneumonitis is suspected, an X-ray examination of the lungs and a study of pulmonary function should be performed.

Radiological manifestations in the initial stage of interstitial pneumonitis can be difficult to distinguish from congestion caused by left ventricular heart failure. If necessary, an additional examination should be performed (for example, determining the pulmonary wedge pressure using a Swan-Ganz catheter), and also exclude other possible causes of shortness of breath and other symptoms (infectious diseases of the lower respiratory tract, pulmonary embolism, malignant neoplasms, etc.). ). Interstitial pneumonitis is usually reversible with early discontinuation of amiodarone, with or without corticosteroid therapy. Clinical symptoms usually resolve within 3-4 weeks.

Improvement in X-ray patterns and lung function occurs more slowly (over several months). In some cases, despite discontinuation of amiodarone, lung damage remains irreversible.

In selected patients, after resolution of interstitial pneumonitis, resumption of amiodarone therapy at lower doses did not lead to recurrence of pulmonary toxicity.

Regardless of the presence or absence of symptoms of lung damage during treatment with Cordarone®, it is recommended to conduct an X-ray examination of the lungs and pulmonary function tests every 6 months.

In patients taking Cordarone®, in very rare cases, usually immediately after surgery, a serious respiratory complication (acute adult respiratory distress syndrome), sometimes fatal, has been observed; the possibility of a connection between its development and interaction with high oxygen concentrations is assumed.

Liver disorders

Various liver diseases (including jaundice, hepatitis, cirrhosis and liver failure) have been observed with the use of amiodarone. Severe liver damage with a fatal outcome has been observed mainly with long-term use of amiodarone, but in rare cases it can develop a short time after the start of treatment (especially with intravenous administration of the drug). It is recommended to evaluate the activity of liver transaminases (AST and ALT) and other indicators of liver function before starting amiodarone, as well as regular monitoring of liver function tests (monitoring the activity of liver transaminases) during treatment and for 6 months after its cessation .

If the activity of “liver” transaminases is 3 times or more higher than the upper limit of normal (ULN), the dose of amiodarone should be reduced or the drug should be stopped.

At the beginning of therapy, an isolated increase in the activity of “liver” transaminases from 1.5 to 3 slots above ULN may be observed. In such cases, liver function tests may return to normal values after reducing the dose of amiodarone.

In case of development of acute liver damage (increased activity, “liver” transaminases and/or jaundice), the use of the drug should be discontinued.

When using amiodarone for more than 6 months, the development of chronic liver damage has been described, which can be manifested by minimally expressed clinical signs (hepatomegaly) and changes in laboratory parameters (increased activity of “liver” transaminases from 1.5 to ≤ 5 times the ULN). Histological examination of liver biopsies reveals changes similar to alcoholic hepatitis or signs of cirrhosis. In such cases, regular monitoring of liver function tests is necessary. Typically, these clinical and laboratory changes are reversible and regress after discontinuation of amiodarone, but cases of progression to liver damage with fatal outcome have been reported.

Due to the potential risk of hepatotoxicity, Cordarone® should be used with extreme caution in patients with impaired liver function. During treatment, it is recommended to exclude (or at least limit) alcohol intake.

Skin and subcutaneous tissue disorders

Life-threatening or even fatal skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with amiodarone use. Treatment with Cordarone® should be stopped immediately if a progressive skin rash, often with blistering, or damage to the mucous membranes appears. Amiodarone quite often causes photosensitivity. Patients should be warned to avoid exposure to direct sunlight or to take protective measures (eg, use of sunscreen, wearing appropriate clothing) during treatment.

Not th p muscle disorders

Cordarone® may cause peripheral sensorimotor neuropathy and/or myopathy. Recovery usually occurs within a few months after discontinuation of Cordarone®, but may sometimes be incomplete.

Drug interactions

The simultaneous use of the drug Cordarone® with the following drugs is not recommended: beta-blockers, blockers of “slow” calcium channels that slow down the heart rate (verapamil, diltiazem); laxatives that stimulate intestinal motility (can cause hypokalemia).

Primary graft dysfunction (PGD) within 24 hours after heart transplantation

The use of amiodarone before heart transplantation is associated with an increased risk of developing PDT (data from retrospective studies).

PTD is a life-threatening complication of heart transplantation, manifesting as dysfunction of the left, right, or both ventricles, and developing within 24 hours after heart transplantation for which no other cause has been identified.

In patients on the waiting list for heart transplantation, the possibility of using an alternative antiarrhythmic drug should be assessed as early as possible.

General and local anesthesia

Before surgery, you should inform the anesthesiologist that the patient is taking the drug Cordarone®. While taking the drug Cordarone®, it is possible to increase the hemodynamic risks inherent in local or general anesthesia (this especially applies to a slowdown in heart rate, slower conduction and decreased contractility of the heart).

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.

Instructions for use CORDARONE®

An ECG must be performed before starting treatment. In older patients, heart rate may decrease more markedly. 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 rather than toxicity.

The drug should be discontinued in case of development of AV blockade of the second and third degrees, sinoatrial block or bifascicular block. In case of development of AV block of the first degree, monitoring should be intensified. There are reports of the emergence of new types of rhythm disturbances or the worsening of existing ones. The arrhythmogenic effect of amiodarone is minor, less than that of most antiarrhythmic drugs, and usually occurs in combination with certain drugs or in cases of electrolyte imbalance.

Amiodarone contains iodine and may therefore 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, serum TSH levels should be measured before starting treatment, regularly (eg every 6 months) during treatment and several months after treatment. If thyroid dysfunction is suspected during treatment with amiodarone, TSH levels should also be measured.

Episodes of dyspnea or dry cough may be associated with pulmonary toxicity, such as the development of interstitial pneumonitis. Patients who have experienced episodes of dyspnea after exercise, as the only symptom or against the background of a deterioration in the patient's general condition (fatigue, weight loss and fever), should undergo chest fluorography. Continued treatment with amiodarone should be considered, as interstitial pneumonitis is often reversible with early discontinuation of amiodarone (clinical symptoms resolve within 3-4 weeks, radiological changes and improvement in pulmonary function are observed within several months). The use of corticosteroids should be assessed. In very rare cases, severe respiratory complications, sometimes fatal (acute respiratory distress syndrome in adults), have been reported, 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..

Acute (severe hepatocellular liver failure or liver damage, sometimes fatal) or chronic liver dysfunction may occur with oral therapy; in this regard, it is recommended to reduce the dose of amiodarone or discontinue 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 during oral therapy can be mild in severity (liver enlargement, transaminase levels 5 times higher than normal) and reversible when treatment with the drug is discontinued, but deaths have also been reported.

Amiodarone may cause sensory, motor or mixed peripheral neuropathies and myopathies.

Resolution of symptoms is usually observed within several months after discontinuation of amiodarone treatment, but some symptoms may persist.

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

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

Combination with verapamil or diltiazem can only be used in the case of prevention of 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 minimum effective therapeutic dose should be used. Patients should be advised to avoid sunlight and use sun protection measures during treatment.

Before starting amiodarone, it is recommended to obtain an ECG and measure serum potassium levels. During treatment, it is recommended to monitor transaminase levels and ECG.

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

Increases in ventricular defibrillation and/or pacemaker or implantable electrical defibrillator pacing threshold have been reported, potentially affecting the efficacy of the drug, particularly in the context of long-term use of antiarrhythmic agents. In this regard, before and during treatment with amiodarone, periodic checks of the operation of the device used should be performed.

Amiodarone contains iodine and may therefore 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 may cause local biochemical changes in patients with normal thyroid function (increased free T4 levels while slightly decreasing or even maintaining normal free T3 levels). 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, decreased activity, excessive bradycardia. The diagnosis is confirmed by a marked increase in serum TSH levels. Restoration of thyroid function to normal usually occurs within 1-3 months after discontinuation of therapy. In life-threatening cases, amiodarone therapy can 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 medicine contains lactose monohydrate (71 mg). The drug should not be taken by patients with hereditary lactose intolerance, galactose intolerance or glucose-galactose malabsorption.

Use in pediatrics

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

Impact on the ability to drive vehicles and operate machinery

The ability to drive vehicles or operate machinery may be impaired if visual impairment occurs as a result of taking amiodarone.

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.

Instructions for use CORDARON, p-d/injections

Contraindicated combinations:

When taking Cordarone simultaneously with antiarrhythmic drugs (including class IA and III drugs, bepridil) as well as with cisapride, difemanil, erythromycin for intravenous administration, mizolastine, vincamycin for intravenous administration, moxifloxacin, spiramycin for intravenous administration, sultopride increases the risk of developing ventricular arrhythmias, especially ventricular tachycardia of the “pirouette” type. Therefore, these combinations are contraindicated.

Undesirable combinations:

When Cordarone and cyclosporine are co-administered, the risk of nephrotoxicity of cyclosporine increases due to an increase in its concentration in plasma and a decrease in metabolism in the liver. If it is necessary to prescribe this combination of drugs, dynamic monitoring of renal function and dose adjustment of cyclosporine during the use of amiodarone and after its discontinuation are necessary.

When Cordarone and diltiazem are co-administered (with intravenous administration of diltiazem), the risk of bradycardia and AV block increases, especially in elderly patients. If it is necessary to prescribe this combination of drugs, dynamic clinical observation and ECG monitoring are necessary.

When Cordarone is used together with halofantrine, pentamidine, lumefantrine, the risk of ventricular arrhythmias, especially ventricular tachycardia of the “pirouette” type, increases. If possible, Cordarone should be discontinued. If necessary, use this combination should be dynamically monitored QT interval.

When Cordarone is co-administered with antipsychotics from the groups of phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), pimozide, the risk of developing ventricular arrhythmias, especially ventricular tachycardia, increases "pirouette" type.

Combinations requiring caution:

Combination therapy with beta-blockers is not recommended, because Automaticity disorders (manifested by bradycardia) and conduction may develop. If it is necessary to prescribe beta-blockers, dynamic ECG monitoring should be performed.

When Cordarone is used simultaneously with anticoagulants for oral administration, the risk of bleeding increases (therefore, it is necessary to monitor the level of prothrombin, INR and adjust the dose of anticoagulants).

With the simultaneous use of Cordarone with cardiac glycosides, disturbances in automaticity (manifested by severe bradycardia) and disturbances in atrioventricular conduction 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 monitor the concentration of digoxin in the blood plasma, perform an ECG and, if necessary, change the dosage regimen).

When Cordarone and diltiazem are co-administered (when diltiazem is taken orally), the risk of developing bradycardia and AV block increases (especially in elderly patients). When prescribing this combination of drugs, dynamic clinical observation and ECG monitoring are necessary.

Cordarone and esmolol should be prescribed with caution, since this combination leads to impaired contractility, automaticity and conduction (due to the suppression of compensatory sympathetic mechanisms). When prescribing these drugs, it is recommended to carry out clinical dynamic observation and ECG monitoring.

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

Cordarone should be used with caution simultaneously with drugs that cause hypokalemia (potassium-removing diuretics, systemic corticosteroids, laxatives that stimulate intestinal motility, tetracosactide, amphotericin B /for intravenous administration/), because the risk of developing arrhythmias increases, especially ventricular tachycardia of the “pirouette” type. If it is necessary to use these groups of drugs, dynamic ECG monitoring and monitoring of potassium levels in the blood serum should be carried out.

When Cordarone and lidocaine are prescribed together, an increase in the concentration of the latter in the blood plasma is observed, which leads to a decrease in the metabolism of lidocaine in the liver and is manifested by an increased likelihood of developing side effects from the central nervous system and the cardiovascular system. Clinical observation, ECG monitoring and, if necessary, dose adjustment of lidocaine are recommended.

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

With simultaneous use of Cordarone with orlistat, there is a risk of reducing the concentration of amiodarone and its active metabolite in plasma. When prescribing this combination, dynamic ECG monitoring is necessary.

Combinations to consider:

Cordarone should be prescribed with caution in combination with drugs that can cause bradycardia (calcium channel blockers / verapamil /, clonidine, guanfacine, mefloquine, cholinesterase inhibitors / donezepil, galantamine, rivastigmine, tacrine, ambemonium, pyridostigmine, neostigmine/, pilocarpine), because To. when prescribing these combinations, there is a risk of excessive bradycardia due to the cumulative effect.

When using oxygen therapy in the postoperative period in patients receiving Cordarone, rare cases of severe respiratory complications, sometimes resulting in death (acute adult respiratory distress syndrome), have been described.

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.