Maximum dose of cordarone per day. Cordarone instructions for use, contraindications, side effects, reviews

Compound

Description of the dosage form

Pills: round, white to off-white in color, with a break line on one side and chamfered 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.

pharmachologic effect

pharmachologic effect- antiarrhythmic.

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 (blockade of potassium channels), it has the effects of class I antiarrhythmics (sodium channel blockade), class IV antiarrhythmics (blockade of calcium channels) and non-competitive beta-adrenergic blocking action.

In addition to the antiarrhythmic effect, it has antianginal, coronary dilation, alpha and beta adrenergic blocking effects.

Antiarrhythmic properties:

Increasing 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);

Reducing automaticity 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 conduction;

An increase in refractory periods and a decrease in the excitability of the myocardium of the atria and ventricles, as well as an increase in the refractory period of the AV node;

Slowing down of conduction and increasing the duration of the refractory period in additional atrioventricular conduction bundles.

Other effects:

No negative inotropic effect when taken orally and parenteral administration;

Reducing myocardial oxygen consumption due to a moderate decrease peripheral resistance and heart rate, as well as myocardial contractility due to the beta-adrenergic blocking effect;

Increased coronary blood flow due to a direct effect on the smooth muscle of the coronary arteries;

Maintenance cardiac output by reducing pressure in the aorta and reducing peripheral resistance;

Effect on the exchange of thyroid hormones: inhibition of the conversion of T 3 to T 4 (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 therapeutic effect usually develops a week after starting to take 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 using isoenzymes CYP3A 4 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 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 interaction of amiodarone with substrates of CYP3A4 isoenzymes has been observed, CYP2C9, CYP2D6 and P-gp.

The elimination of amiodarone begins within a few days, and the achievement of equilibrium between the intake and elimination of the drug (achievement of an equilibrium state) occurs after one to several months, depending on the individual characteristics of the patient. The main route of 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, you should remember that it is necessary to at least 1 month 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 a long oral administration average T 1/2 - 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 at daily dose amiodarone 200 mg). Most of iodine remaining in the composition of the drug is excreted from 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.

When Cordarone ® is administered intravenously, 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 the drug Cordarone ®

Pills

Relapse prevention:

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

supraventricular paroxysmal tachycardia: documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with organic heart disease; documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients without organic heart disease, when antiarrhythmic drugs other classes are not effective or there are contraindications to their use; documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome;

atrial fibrillation(atrial fibrillation) and atrial flutter.

prevention of sudden arrhythmic death in patients of the group high risk: after a recent myocardial infarction with more than 10 ventricular extrasystoles at 1 o'clock, clinical manifestations 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.

Injection form of Cordarone ®

relief of attacks of ventricular paroxysmal tachycardia; supraventricular paroxysmal tachycardia with high frequency 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 drug;

sick sinus syndrome ( sinus bradycardia, sinoatrial block), with the exception of cases of correction with an artificial pacemaker (danger of “stopping” the sinus node).

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 (see “Interaction”):

Antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide procainamide); class III antiarrhythmic drugs (dofetilide, ibutilide, bretylium tosylate); sotalol;

Other (non-antiarrhythmic) drugs such as bepridil; vincamine; some 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 for intravenous administration, spiramycin); azoles; antimalarials (quinine, chloroquine, mefloquine, halofantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones.

congenital or acquired prolongation of the QT interval.

dysfunction thyroid gland(hypothyroidism, hyperthyroidism).

pregnancy (see “Use during pregnancy and lactation”);

lactation period (see “Use during pregnancy and lactation”);

age under 18 years (efficacy and safety have not been established).

For tablets additionally: interstitial lung disease.

For 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 cases of arterial hypotension, severe respiratory failure, cardiomyopathy or heart failure (these conditions may become more severe).

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.

Carefully used for 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 of the first degree.

Use during pregnancy and breastfeeding

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 more early use. Excess iodine when using the drug after this period can lead to the appearance of laboratory symptoms hypothyroidism in a newborn or even the formation of a clinically significant goiter.

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

Lactation period

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

Side effects

Frequency side effects was defined as follows: very often - ≥10%), often - ≥1%,<10; нечасто — ≥0,1%, <1%; редко — ≥0,01%, <0,1% и очень редко, включая отдельные сообщения — <0,01%, частота не известна (по имеющимся данным частоту определить нельзя).

Pills.

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 in cases where Cordarone ® is used in conjunction with drugs that prolong the period of repolarization of the ventricles of the heart (QT c interval) or in case of electrolyte imbalance (see “Interaction”). 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).

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 (see "Special Instructions"). 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.

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 (possibility of interaction with high doses of oxygen is expected) (see "Special Instructions"). 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 the detection of elevated serum TSH levels. 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 the 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.

Others: very rarely - vasculitis, epididymitis, several cases of impotence (no relationship 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 (QT 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 (possibility of interaction with high concentrations of oxygen is expected) (see "Special Instructions").

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 (see "Special Instructions").

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

From 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.

Interaction

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, which 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).

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 the 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 within 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 within 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 taken intermittently 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 impossible.

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 ®, only a 5% dextrose (glucose) solution should be used. 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 ) (see “Special instructions”).

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, if possible, using an electronic pump 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 jet administration (see “Special Instructions”)

The first dose is 300 mg (or 5 mg/kg) of cordarone, after dilution 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.

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. Atrioventricular conduction may slow down and pre-existing heart failure may worsen.

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.There is no specific antidote.

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

special instructions

Pills

Since the side effects of amiodarone are dose-related, patients should be treated with the lowest effective doses to minimize the possibility of their occurrence.

Patients should be warned to avoid exposure to direct sunlight or take protective measures (eg using sunscreen, wearing appropriate clothing) during treatment.

Treatment monitoring

Before starting amiodarone, it is recommended to conduct an ECG study and determine the level of potassium in the blood. Hypokalemia should be corrected before starting amiodarone. During treatment, it is necessary to regularly monitor the ECG (every 3 months), transaminase levels and other indicators of liver function.

In addition, due to the fact that amiodarone can cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, before taking amiodarone, a clinical and laboratory (TSH) examination should be performed to identify dysfunctions and diseases of the thyroid gland. During treatment with amiodarone and for several months after its cessation, the patient should be regularly monitored for clinical or laboratory signs of changes in thyroid function. If thyroid dysfunction is suspected, it is necessary to determine the level of TSH in the blood serum.

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

In patients receiving long-term treatment for arrhythmias, cases of increased frequency of ventricular fibrillation and/or increased threshold for the response of a pacemaker or implanted defibrillator have been reported, which may reduce their effectiveness. Therefore, before starting or during treatment with amiodarone, the correct functioning of these devices should be checked regularly.

The appearance of shortness of breath or a dry cough, either isolated or accompanied by a deterioration in general condition, should indicate the possibility of pulmonary toxicity, such as interstitial pneumopathy, the suspicion of which requires X-ray examination of the lungs and pulmonary function tests.

Due to the prolongation of the period of repolarization of the ventricles of the heart, the pharmacological action of Cordarone ® causes certain ECG changes: prolongation of the QT interval, QT s (corrected), the appearance of U waves is possible. An increase in the QT interval s is permissible by no more than 450 ms or by no more than 25% of the original value . These changes are not a manifestation of the toxic effect of the drug, but require monitoring to adjust the dose and assess the possible proarrhythmogenic effect of Cordarone ®.

If II and III degree AV block, sinoatrial block or double-fascicular intraventricular block develops, treatment should be discontinued. If 1st degree AV block occurs, monitoring should be intensified.

Although the occurrence of arrhythmia or worsening of existing rhythm disturbances has been noted, it should be noted that the proarrhythmogenic effect of amiodarone is weak and usually occurs in combination with certain drugs or in cases of electrolyte imbalance.

If vision is blurred or visual acuity is reduced, an ophthalmological examination, including fundus examination, should be performed. If neuropathy or optic neuritis caused by amiodarone develops, the drug must be discontinued due to the risk of blindness.

Since Cordarone ® contains iodine, its intake may distort the results of a radioisotope study of the thyroid gland, but does not affect the reliability of the determination of the content of T 3, T 4 and TSH in the blood plasma.

Before surgery, the anesthesiologist should be informed that the patient is receiving Cordarone ® .

Long-term treatment with Cordarone ® may increase the hemodynamic risk inherent in local or general anesthesia. This particularly applies to its bradycardic and hypotensive effects, decreased cardiac output and conduction disturbances.

In addition, in rare cases, acute respiratory distress syndrome was observed in patients receiving Cordarone ® immediately after surgery. During artificial ventilation of the lungs, such patients require careful monitoring.

Injection

IV jet administration should be carried out only in emergency cases when other types of treatment are ineffective and only in the intensive care unit under constant monitoring of ECG and blood pressure. The dose is 5 mg/kg. Except in cases of cardiac resuscitation for ventricular fibrillation resistant to defibrillation, IV bolus administration of amiodarone should be administered for at least 3 minutes. Repeated administration of amiodarone should not be carried out earlier than 15 minutes after the first injection, even if the contents of only one ampoule were administered during the first injection (the possibility of irreversible collapse).

If there is a need for continued administration of amiodarone, it should be administered as an infusion.

In order to avoid reactions at the injection site (see “Side Effects”), the injection form of Cordarone ® is recommended to be administered through a central venous catheter. Only in the case of cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to cardioversion, in the absence of central venous access (no central venous catheter in place), the injectable form of Cordarone ® can be administered into a large peripheral vein with maximum blood flow.

If treatment with Cordarone ® must be continued after cardiac resuscitation, the drug should be administered intravenously through a central venous catheter under constant monitoring of blood pressure and ECG.

Cordarone ® cannot be mixed in the same syringe or dropper with other drugs.

Due to the possibility of the development of interstitial pneumonitis when severe shortness of breath or dry cough appears after the administration of Cordarone ®, both accompanied and not accompanied by a deterioration in the general condition (increased fatigue, fever), it is necessary to perform a chest x-ray and, if necessary, discontinue the drug, t .To. interstitial pneumonitis can lead to the development of pulmonary fibrosis. However, these effects are generally reversible with early discontinuation of amiodarone with or without the administration of corticosteroids. Clinical manifestations usually disappear within 3-4 weeks. Recovery of the X-ray picture and lung function occurs more slowly (several months).

After artificial ventilation of the lungs (for example, during surgical interventions), rare cases of acute respiratory distress syndrome, sometimes fatal, have been observed in patients who were administered Cordarone ® (possibility of interaction with high doses of oxygen is expected) (see “Side effects”). Therefore, it is recommended to strictly monitor the condition of such patients.

During the first 24 hours after starting to use the injection form of Cordarone ®, severe acute liver damage may develop with the development of liver failure, sometimes with a fatal outcome. Regular monitoring of liver function is recommended during treatment with Cordarone ® .

General anesthesia

Before surgery, the anesthesiologist should be informed that the patient is receiving Cordarone ® . Treatment with Cordarone ® may increase the hemodynamic risk inherent in local or general anesthesia. This particularly applies to its bradycardic and hypotensive effects, decreased cardiac output and conduction disturbances.

Combinations with beta-blockers other than sotalol (a contraindicated combination) and esmolol (a combination requiring special caution when used), verapamil and diltiazem can only be considered in the context of the prevention of life-threatening ventricular arrhythmias and in the case of cardiac restoration in cardiac arrest caused by fibrillation ventricles resistant to cardioversion.

Electrolyte disturbances, especially hypokalemia: It is important to consider situations that may be accompanied by hypokalemia as predisposing to proarrhythmic events. Hypokalemia must be corrected before using Cordarone ® .

Side effects of the drug (see "Side Effects") are usually dose dependent; Therefore, care should be taken when determining the minimum effective maintenance dose to avoid or minimize the occurrence of adverse effects.

Amiodarone may cause thyroid dysfunction, especially in patients with a personal or family history of thyroid dysfunction. Therefore, in case of switching to taking Cordarone ® orally, during treatment and several months after the end of treatment, careful clinical and laboratory monitoring should be carried out. If thyroid dysfunction is suspected, serum TSH levels should be determined.

The safety and effectiveness of amiodarone have not been studied in children. Cordarone ® injection ampoules contain benzyl alcohol. Severe choking with fatal outcome has been reported in newborns after intravenous administration of solutions containing benzyl alcohol.

Influence on the ability to drive a car and other mechanisms. During treatment with Cordarone ® you should refrain from driving a car and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Release form

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.

Manufacturer

Sanofi Winthrop Industrie, 1, rue de la Vierge, Ambares et Lagrave, 33565 Carbon Blanc, France.

HINOIN Pharmaceutical and Chemical Products Plant CJSC st. Levai 5, 2112, Veresedház, Hungary.

Conditions for dispensing from pharmacies

On prescription.

Storage conditions for the drug Cordarone ®

At a temperature not exceeding 30 °C.

Keep out of the reach of children.

Shelf life of the drug Cordarone ®

solution for intravenous administration 50 mg/ml - 2 years.

tablets 200 mg - 3 years.

Do not use after the expiration date stated on the package.

Synonyms of nosological groups

Category ICD-10	Synonyms of diseases according to ICD-10
I47.1 Supraventricular tachycardia	Supraventricular paroxysmal tachycardia
	Supraventricular tachyarrhythmia
	Supraventricular tachycardia
	Supraventricular arrhythmias
	Supraventricular paroxysmal tachycardia
	Supraventricular tachyarrhythmias
	Supraventricular tachycardia
	Neurogenic sinus tachycardia
	Orthodromic tachycardia
	Paroxysmal supraventricular tachycardia
	Paroxysm of supraventricular tachycardia
	Paroxysm of supraventricular tachycardia in WPW syndrome
	Paroxysm of atrial tachycardia
	Paroxysmal supraventricular tachyarrhythmia
	Paroxysmal supraventricular tachycardia
	Polytopic atrial tachycardia
	Atrial arrhythmia
	Atrial true tachycardia
	Atrial tachycardia
	Atrial tachycardia with AV block
	Reperfusion arrhythmia
	Berzold-Jarisch reflex
	Recurrent sustained supraventricular paroxysmal tachycardia
	Symptomatic ventricular tachycardias
	Wolff-Parkinson-White syndrome
	Sinus tachycardia
	Supraventricular paroxysmal tachycardia
	Supraventricular tachyarrhythmia
	Supraventricular tachycardia
	Supraventricular extrasystole
	Supraventricular arrhythmias
	Tachycardia from AV junction
	Supraventricular tachycardia
	Tachycardia orthodromic
	Sinus tachycardia
	Junctional tachycardia
	Chaotic polytopic atrial tachycardia
I47.2 Ventricular tachycardia	Ventricular arrhythmia
	Ventricular paroxysmal tachycardia
	Ventricular tachyarrhythmia
	Ventricular tachycardia
	Paroxysmal bidirectional fusiform ventricular tachycardia
	Paroxysmal ventricular tachycardia
	Torsade de pointes (torsade de pointes)
	Torsades de pointes in myocardial infarction
	Symptomatic ventricular tachycardia
	Ventricular tachycardia
	Life-threatening ventricular arrhythmia
	Sustained ventricular tachycardia
	Sustained monomorphic ventricular tachycardia
I48 Atrial fibrillation and flutter	Stopping rapid ventricular rhythm during atrial fibrillation or flutter
	Atrial fibrillation
	Supraventricular arrhythmia
	Paroxysm of atrial fibrillation and flutter
	Paroxysm of atrial fibrillation
	Paroxysmal form of atrial fibrillation and flutter
	Paroxysmal atrial fibrillation and flutter
	Paroxysmal atrial fibrillation
	Permanent form of atrial fibrillation
	Atrial extrasystole
	Atrial extrasystoles
	Tachyarrhythmic form of atrial fibrillation
	Tachysystolic form of atrial fibrillation
	Atrial flutter

	Atrial fibrillation
	Chronic atrial fibrillation
I49.0 Ventricular fibrillation and flutter	Ventricular fibrillation

	Ventricular flutter
	Life-threatening ventricular fibrillation
	Ventricular fibrillation
I49.3 Premature ventricular depolarization	Ventricular arrhythmia
	Asynergy of the ventricles of the heart
	Left ventricular asynergia
	Pronounced ventricular extrasystoles
	Ventricular arrhythmia
	Ventricular extrasystole
	Ventricular extrasystole
	Ventricular arrhythmias
	Ventricular extrasystoles
	Paroxysmal ventricular extrasystole
	Recurrent ventricular arrhythmias
	Ventricular extrasystole
I49.8 Other specified cardiac arrhythmias	Arrhythmia atrial fibrillation
	Paroxysmal atrial fibrillation
	Arrhythmia atrial fibrillation tachysystolic
	Sinus arrhythmia
	Asynergy of the ventricles of the heart
	Left ventricular asynergia
	Bigeminy
	Corrigan pulse
	Atrial fibrillation
	Atrial tachyarrhythmia
	Migration of the supraventricular pacemaker
	Orthostatic heart rate changes
	Sinoatrial node failure
	Paradoxical pulse
	Paroxysm of atrial fibrillation
	Paroxysmal atrial fibrillation
	Paroxysmal rhythm disorder
	Paroxysmal atrioventricular rhythm
	Romano-Ward syndrome
	Trigeminy
I51.9 Heart disease, unspecified	Heart diseases
	Cardiac decompensation
	Heart disease
	Non-atherosclerotic lesions of the coronary arteries
	Fainting due to heart disease
	Organic heart disease
	Acute decompensated heart failure
	Acquired heart defect
	Heart attack
	Chronic heart disease

Cordarone (active ingredient - amiodarone) is an antiarrhythmic drug from one of the world's leading pharmaceutical corporations, Sanofi Aventis. This drug has been used in clinical practice for more than 50 years and has a truly unique range of pharmacological effects. Cordarone was originally synthesized as a coronary vasodilator for the treatment of angina pectoris. This was in tune with the prevailing ideas at that time about what an ideal antianginal drug should be. However, as it was later found out, the antianginal effect of cordarone is associated not so much with its coronary-dilating effect as with the blockade of myocardial beta-adrenergic receptors. As a result, cordarone is not widely used as an antianginal drug due to poorer tolerability compared to beta blockers and calcium antagonists. Bad luck began: at the end of the 60s of the last century, the antiarrhythmic effect of cordarone was discovered, and the peculiarities of the electrophysiological properties of the drug made it possible to classify it as a new third class of antiarrhythmic drugs at that time. Today, this drug is one of the most commonly and successfully used drugs in the treatment of ventricular and atrial arrhythmias.

The uniqueness of cordarone lies in the fact that in addition to the “standard” properties of class III antiarrhythmic drugs (potassium channel blocking), it accumulates the effects of class I (sodium channel blocking) and class IV antiarrhythmic drugs (calcium channel blocking).

In addition to this, it has the beta-adrenergic blocking effect already mentioned at the beginning of the article. Thus, cordarone is an effective antiarrhythmic agent with a wide range of therapeutic effects. It successfully eliminates ventricular and supraventricular tachyarrhythmias and maintains sinus rhythm in patients with atrial flutter and fibrillation. Cordarone effectively prevents sudden death in patients with heart failure or who have had a myocardial infarction.

Cordarone is available in the form of tablets and solution for intravenous administration. The tablets should be taken before meals with sufficient liquid. The tactics of oral administration of cordarone include a saturation period and a maintenance period. The saturating (loading) dose ranges from 600 to 800 mg per day until a total dose of 10 g is reached (this usually takes 10–14 days). The maintenance dose ranges from 100 to 400 mg per day. Given the long half-life of cordarone, it is not necessary to take it every day (for example, every other day). On average, a single dose of the drug is 200 mg, a daily dose is 400 mg, with a set maximum of 1200 mg. The injection form of cordarone is used only in cases where the speed of implementation of the antiarrhythmic effect is of great importance or if oral administration of the drug is not possible.

Pharmacology

Antiarrhythmic drug. Amiodarone belongs to class III (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, the drug has antianginal, coronary dilation, alpha and beta adrenergic blocking effects.

Antiarrhythmic action:

an increase in the duration of phase 3 of the action potential of cardiomyocytes, mainly due to blocking the ion current in potassium channels (the effect of class III antiarrhythmics according to the Williams classification);
decreased automatism of the sinus node, leading to a decrease in heart rate;
non-competitive blockade of α- and β-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 AV conduction bundles.

Other effects:

lack of negative inotropic effect when taken orally;
reduction of oxygen consumption by the myocardium due to a moderate decrease in peripheral vascular resistance and heart rate;
an increase in coronary blood flow due to a direct effect on the smooth muscle of the coronary arteries;
maintaining cardiac output by reducing pressure in the aorta and reducing peripheral vascular 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.

After starting to take the drug orally, the therapeutic effects develop on average within a week (from several days to 2 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

Suction

Bioavailability after oral administration varies from 30% to 80% in different patients (average value about 50%). After a single oral dose of amiodarone, Cmax in blood plasma is reached within 3-7 hours. However, the therapeutic effect usually develops a week after starting the drug (from several days to 2 weeks).

Distribution

Binding to plasma proteins is 95% (62% to albumin, 33.5% to beta-lipoproteins). Amiodarone has a large Vd. Amiodarone is characterized by slow release into tissues and high affinity for them. 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.

Metabolism

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 CYP1A1, CYP1A2, 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.

Removal

Amiodarone elimination begins within a few days, and achieving equilibrium between the intake and elimination of the drug (achieving C ss) 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. 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.

The pharmacokinetic features of the drug explain the use of loading doses, which is aimed at the rapid accumulation of amiodarone in tissues, at which its therapeutic effect is manifested.

Pharmacokinetics in special clinical situations

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

Release form

Tablets are white to off-white in color, round, with a break line on one side, beveled from the edges to the break line and chamfered on both sides, engraved with a heart symbol above the break line and the number “200” below the break line.

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

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

Dosage

The drug should be taken only as prescribed by a doctor.

Cordarone ® tablets are taken orally before meals and washed down with a sufficient amount of water.

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

In the hospital: the initial dose, divided into several doses, ranges from 600-800 mg (up to a maximum of 1200 mg) / day until a total dose of 10 g is reached (usually within 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 within 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 effect.

Because Cordarone ® has a very large T1/2, 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.

Overdose

Symptoms: When ingesting very large doses, several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal ventricular tachycardia of the "pirouette" type and liver damage have been described. Possible slowdown of AV conduction, worsening of existing heart failure.

Treatment: gastric lavage, use 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 ventricular tachycardia of the "pirouette" type - intravenous administration of magnesium salts or cardiac stimulation.

Neither amiodarone nor its metabolites are removed by hemodialysis. There is no specific antidote.

Interaction

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

Drugs that can cause torsade de pointes (TdP)

Combination therapy with drugs that can cause ventricular tachycardia of the "pirouette" type is contraindicated, because the risk of developing potentially fatal torsade de pointes (TdP) increases. These include:

antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide, procainamide), sotalol, bepridil;
other (non-antiarrhythmic) drugs such as 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 ratio of expected benefit and potential risk (the possibility of an increased risk of developing torsade de pointes); when using such combinations, it is necessary to constantly monitor the ECG of patients (for detection of QT interval prolongation), potassium and magnesium content in the blood.

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

Drugs that slow the heart rate or cause problems with automaticity or conduction

Combination therapy with these drugs is not recommended.

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

Drugs that can cause hypokalemia

with laxatives that stimulate intestinal motility, which can cause hypokalemia, which increases the risk of developing torsades de pointes. When combined with amiodarone, laxatives from other groups should be used.

Combinations requiring caution when using

with diuretics that cause hypokalemia (in monotherapy or in combination with other drugs);
with systemic corticosteroids (glucocorticoids, mineralocorticoids), tetracosactide;
with 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), and in the event of ventricular tachycardia of the “pirouette” type, antiarrhythmic drugs should not be used (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 taking amiodarone during general anesthesia has been reported: bradycardia (resistant to atropine), decreased blood pressure, conduction disturbances, 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, and the occurrence of which is associated with high oxygen concentrations).

Drugs that reduce heart rate (clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine

Risk of developing excessive bradycardia (cumulative effects).

Effect of amiodarone on other drugs

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

Drugs that are P-gp substrates

Amiodarone is a P-gp inhibitor. It is expected that its combined use with drugs that are P-gp substrates will lead to increased systemic exposure of the latter.

Cardiac glycosides (digitalis preparations)

Possibility of disturbances in automaticity (severe bradycardia) and atrioventricular conduction. In addition, when combining digoxin with amiodarone, an increase in the concentration of digoxin in the blood plasma is possible (due to a decrease in its clearance). Therefore, when combining digoxin with amiodarone, it is necessary to determine the concentration of digoxin in the blood and monitor possible clinical and electrocardiographic manifestations of digitalis intoxication. Digoxin dosages may need to be reduced.

Dabigatran

Caution should be exercised when amiodarone is used concomitantly with dabigatran due to the risk of bleeding. The dose of dabigatran may need to be adjusted in accordance with the instructions in its instructions for use.

Medicines that are substrates of the CYP2C9 isoenzyme

Amiodarone increases the blood concentration of drugs that are substrates of the CYP2C9 isoenzyme, such as warfarin or phenytoin due to inhibition of cytochrome P450 2C9.

Warfarin

When warfarin is combined with amiodarone, the effects of the indirect anticoagulant may be enhanced, which increases the risk of bleeding. Prothrombin time should be monitored more frequently (by determining MHO) and anticoagulant doses adjusted, both during treatment with amiodarone and after discontinuation of its use.

Phenytoin

When combining phenytoin with amiodarone, an overdose of phenytoin may develop, which can lead to the appearance of neurological symptoms; Clinical monitoring and reduction of the dose of phenytoin is necessary at the first signs of overdose; it is advisable to determine the concentration of phenytoin in the blood plasma.

Medicines that are substrates of the CYP2D6 isoenzyme

Flecainide

Amiodarone increases plasma concentrations of flecainide due to inhibition of the CYP2D6 isoenzyme, which requires adjustment of flecainide doses.

Medicines that are substrates of the CYP3A4 isoenzyme

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

Cyclosporine

The combination of cyclosporine with amiodarone may increase plasma concentrations of cyclosporine; dose adjustment is necessary.

Fentanyl

Combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects.

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

Increased risk of statin muscle toxicity when used concomitantly with amiodarone. The use of statins that are not metabolized by the CYP3A4 isoenzyme is recommended.

Other drugs metabolized by CYP3A4: lidocaine (risk of sinus bradycardia and neurological symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (risk of increased side effects), midazolam (risk of psychomotor effects), triazolam, dihydroergotamine, ergotamine, colchicine .

Amiodarone inhibits CYP2D6 and CYP3A4 and may theoretically increase plasma concentrations of dextromethorphan.

Clopidogrel

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

Effect of other drugs on amiodarone

Inhibitors of CYP3A4 and CYP2C8 isoenzymes may have the potential to inhibit the metabolism of amiodarone and increase its concentration in the blood and, accordingly, its pharmacodynamic and side effects.

It is recommended to avoid CYP3A4 inhibitors (eg, grapefruit juice and certain drugs such as cimetidine and HIV protease inhibitors (including indinavir) during therapy with amiodarone. HIV protease inhibitors, when used concomitantly with amiodarone, may increase amiodarone concentrations in blood.

Inducers of the CYP3A4 isoenzyme

Rifampicin

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

Preparations of St. John's wort

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

Side effects

The frequency of side effects was determined according to the WHO classification: very common (≥10%); often (≥1%,<10); нечасто (≥0.1%, <1%); редко (≥0.01%, <0.1%); очень редко, включая отдельные сообщения (<0.01%); частота неизвестна (по имеющимся данным частоту определить нельзя).

From the cardiovascular system: often – bradycardia, usually moderate, the severity of which depends on the dose of the drug; infrequently - conduction disturbance (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); Based on the available data, it is impossible to determine whether the occurrence of these rhythm disturbances is caused by the action of the drug Cordarone ®, the severity of cardiovascular pathology, or is a consequence of treatment ineffectiveness. These effects are observed mainly in cases of use of the drug Cordarone ® in conjunction with drugs that prolong the period of repolarization of the ventricles of the heart (QT interval) or in cases of disturbances in the content of electrolytes in the blood.

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), vasculitis; frequency unknown - progression of chronic heart failure (with long-term use), ventricular tachycardia of the "pirouette" type.

From the digestive system: very often - nausea, vomiting, dysgeusia (dulling or loss of taste), usually occurring when taking a loading dose and disappearing after its reduction.

From the liver and biliary tract: very often - isolated increase in transaminase activity in the blood serum, usually moderate (1.5-3 times higher than normal values; decreases with dose reduction or spontaneously); often - acute liver damage with increased transaminase activity and/or jaundice, including the development of liver failure, sometimes fatal; very rarely - chronic liver diseases (pseudoalcoholic hepatitis, cirrhosis), 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 - pulmonary toxicity, sometimes fatal (alveolar/interstitial pneumonitis or fibrosis, pleurisy, bronchiolitis obliterans with pneumonia). Although these changes can lead to the development of pulmonary fibrosis, they are largely reversible with early discontinuation of amiodarone and with or without the use of 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 taking amiodarone, either accompanied or not accompanied by a deterioration in the general condition (increased fatigue, loss of body weight, increase in 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 oxygen concentrations is expected).

Frequency unknown - pulmonary hemorrhage.

On the part of the organ of vision: 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 impairment in the form of a colored halo or blurriness contours in bright light; very rarely - optic neuritis/optic neuropathy (no relationship with amiodarone has been established to date; however, since optic neuritis can lead to blindness, if blurred vision or decreased visual acuity occurs while taking Cordarone ®, a full ophthalmological examination is recommended, including fundoscopy, and if optic neuritis is detected, stop taking the drug).

From the endocrine system: often - hypothyroidism (weight gain, chilliness, apathy, decreased activity, drowsiness, excessive bradycardia compared to the expected effect of amiodarone). The diagnosis is confirmed by identifying an elevated serum TSH level (using an ultrasensitive TSH test); 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 the control of serum TSH levels.

Hyperthyroidism is also common, sometimes fatal, and may occur during and after treatment (cases of hyperthyroidism developing 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 (using an ultrasensitive TSH test). 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 the myocardial oxygen demand and its delivery, it is recommended to immediately begin treatment: the use of antithyroid drugs (which may not always be effective in this case), treatment with corticosteroids ( 1 mg/kg), which lasts quite a long time (3 months), beta-blockers.

Very rarely - syndrome of impaired secretion of ADH.

From the skin and subcutaneous tissues: very often - photosensitivity; often (in case of prolonged use of the drug in high daily doses) - grayish or bluish pigmentation of the skin (after stopping treatment, this pigmentation slowly disappears); very rarely - erythema (during radiation therapy), skin rash (usually unspecific), alopecia, exfoliative dermatitis, alopecia; frequency unknown - urticaria.

From the nervous system: often - tremor or other extrapyramidal symptoms, sleep disturbances, nightmares; uncommon - sensorimotor peripheral neuropathies and/or myopathy (usually reversible within a few months after discontinuation of the drug, but sometimes not completely); very rarely - cerebellar ataxia, benign intracranial hypertension (pseudotumor cerebri), headache.

From the genital organs and mammary gland: very rarely - epididymitis, impotence.

From the hematopoietic system: very rarely - thrombocytopenia, hemolytic anemia, aplastic anemia.

Allergic reactions: frequency unknown - angioedema (Quincke's edema).

Laboratory and instrumental data: very rarely - an increase in the concentration of creatinine in the blood serum.

General disorders: frequency unknown - granuloma formation, including bone marrow granuloma.

Indications

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

patients after a recent myocardial infarction with more than 10 ventricular extrasystoles per hour, clinical manifestations of chronic heart failure and a reduced left ventricular ejection fraction (less than 40%).

Cordarone ® can be used in the treatment of arrhythmias in patients with coronary artery disease and/or impaired left ventricular function.

Contraindications

SSS (sinus bradycardia, sinoatrial block), except in cases of their correction with an artificial pacemaker (danger of “stopping” the sinus node);
AV blockade of II and III degrees in the absence of an artificial pacemaker (pacemaker);
hypokalemia, hypomagnesemia;
interstitial lung disease;
thyroid dysfunction (hypothyroidism, hyperthyroidism);
congenital or acquired prolongation of the QT interval;
combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including torsades de pointes: class I A antiarrhythmic drugs (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, sulpiride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; antibiotics of the macrolide group (in particular erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones;
age under 18 years (efficacy and safety have not been established);
pregnancy;
lactation period;
lactose intolerance (lactase deficiency), glucose-galactose malabsorption syndrome (the drug contains lactose);
hypersensitivity to iodine, amiodarone or excipients of the drug.

Use with caution in decompensated or severe chronic (III-IV functional class according to the NYHA classification) heart failure, liver failure, bronchial asthma, severe respiratory failure, in elderly patients (high risk of developing severe bradycardia), with 1st degree AV blockade .

Features of application

Use during pregnancy and breastfeeding

Pregnancy

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

Since the fetal thyroid gland begins to bind iodine only from the 14th week of pregnancy (amenorrhea), amiodarone is not expected to affect it 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 risks (in case of life-threatening ventricular arrhythmias).

Breastfeeding period

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

Use for liver dysfunction

Use with caution in case of liver failure.

Use for renal impairment

Insignificant excretion of the drug in the urine allows the drug to be prescribed in moderate doses for renal failure. Amiodarone and its metabolites are not dialyzable.

Use in children

Contraindication: children and adolescents under 18 years of age (efficacy and safety have not been established).

special instructions

Because Side effects of amiodarone are dose-dependent, and patients should be treated with the lowest effective doses to minimize their occurrence.

Patients should be warned to avoid exposure to direct sunlight or to take protective measures (eg, use of sunscreen, wearing appropriate clothing) during treatment.

Treatment monitoring

Before starting amiodarone, it is recommended to conduct an ECG study and determine the potassium level in the blood. Hypokalemia should be corrected before starting amiodarone. During treatment, it is necessary to regularly monitor ECG (every 3 months) and transaminase activity and other indicators of liver function.

In addition, due to the fact that amiodarone can cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, before taking amiodarone, clinical and laboratory (serum TSH concentration determined using an ultrasensitive TSH test) examination should be performed for the subject of identifying dysfunctions and diseases of the thyroid gland. During treatment with amiodarone and for several months after its cessation, the patient should be regularly monitored for clinical or laboratory signs of changes in thyroid function. If thyroid dysfunction is suspected, it is necessary to determine the concentration of TSH in the blood serum (using an ultrasensitive TSH test).

In patients receiving long-term treatment for arrhythmias, an increase in the frequency of ventricular defibrillation and/or an increase in the threshold of the pacemaker or implanted defibrillator has been reported, which may reduce the effectiveness of these devices. Therefore, before starting or during treatment with amiodarone, their correct functioning should be checked regularly.

The appearance of shortness of breath or a dry cough, either isolated or accompanied by a deterioration in general condition (fatigue, weight loss, fever), may indicate pulmonary toxicity such as interstitial pneumonitis, the suspicion of which requires X-ray examination of the lungs and pulmonary function tests. samples

Due to the prolongation of the period of repolarization of the ventricles of the heart, the pharmacological effect of the drug Cordarone ® causes certain ECG changes: prolongation of the QT interval, QT s (corrected), the appearance of U waves is possible. An increase in the QT interval s is permissible by no more than 450 ms or by no more than 25% of the original quantities. These changes are not a manifestation of the toxic effect of the drug, but require monitoring to adjust the dose and evaluate the possible proarrhythmogenic effect of the drug Cordarone ® .

If II and III degree AV block, sinoatrial block or double-bundle intraventricular block develops, treatment should be discontinued. If 1st degree AV block occurs, monitoring should be intensified.

Although the occurrence of arrhythmias or worsening of existing rhythm disturbances, sometimes fatal, has been noted, the proarrhythmogenic effect of amiodarone is mild (less pronounced than most antiarrhythmic drugs) and usually occurs in the context of factors prolonging the QT interval, such as interactions with other drugs and/or in case of disturbances in the content of electrolytes in the blood. Despite the ability of amiodarone to prolong the QT interval, it has shown little activity in inducing torsade de pointes (TdP).

If vision is blurred or visual acuity is reduced, an immediate ophthalmological examination, including fundus examination, is necessary. With the development of neuropathy or optic neuritis caused by amiodarone, the drug must be discontinued due to the risk of blindness.

Since Cordarone ® contains iodine, its use may interfere with the absorption of radioactive iodine and distort the results of a radioisotope study of the thyroid gland, however, taking the drug does not affect the reliability of determining the content of T3, T4 and TSH in the blood plasma. 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 amiodarone.

The development of hypothyroidism can be suspected when the following clinical signs, usually mild, appear: weight gain, cold intolerance, decreased activity, excessive bradycardia.

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

In addition, in rare cases, acute respiratory distress syndrome was observed in patients taking Cordarone ® immediately after surgery. These patients require careful monitoring during mechanical ventilation.

Careful monitoring of liver function tests (determining transaminase activity) is recommended before starting to take the drug Cordarone ® and regularly during treatment with the drug. Acute liver dysfunction (including hepatocellular failure or liver failure, sometimes fatal) and chronic liver damage may occur when taking the drug Cordarone ® . Therefore, treatment with amiodarone should be discontinued when transaminase activity increases to 3 times the ULN.

Clinical and laboratory signs of chronic liver failure when taking amiodarone orally can be minimally expressed (hepatomegaly, increased transaminase activity 5 times the ULN) and reversible after discontinuation of the drug, but cases of death with liver damage have been reported.

Impact on the ability to drive vehicles and operate machinery

Based on safety data, there is no evidence that amiodarone impairs the ability to drive or engage in other potentially hazardous activities. However, as a precautionary measure, it is advisable for patients with paroxysms of severe rhythm disturbances during treatment with Cordarone ® to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Cordarone is a potent antiarrhythmic drug that is used to treat ventricular arrhythmias and atrial fibrillation.

The drug prevents the recurrence of life-threatening cardiac arrhythmias and causes a modest reduction in sudden death in patients at high risk.

Cordarone, instructions for use, prices, reviews and its analogues can be found in articles devoted to the work of this drug.

Cordarone is a complex antiarrhythmic agent (mixture of substances) with multiple electrophysiological effects, unusual pharmacokinetics, and numerous potentially harmful drug interactions and side effects.

The drug includes an iodine-containing compound with some structural similarity to Thyroxine.

The high iodine content in Cordarone is a factor in its effect on the thyroid gland. Cordarone's bioavailability is considered variable, but overall it is quite poor, ranging from 22 to 95%. Absorption is enhanced when the drug is taken with food.

Cordarone is a high-lipid soluble agent. The drug crosses the placenta and reaches measurable levels in breast milk. The main metabolite of Cordarone is desimilamioron, which is known to have antiarrhythmic effects.

The half-life of Cordarone varies widely and is unusually long, averaging about 58 days. The long half-life is thought to result from the slow release of the drug from lipid-rich tissues.

Cordarone is classified as a Class III drug (Vaughan Williams classification), which indicates that it prolongs the QT interval, i.e. the distance from the beginning of the QRS complex to the end of the T wave in the electrocardiogram.

The drug has many other properties - it slows heart rate and atrioventricular nodal conduction through calcium channel and adrenergic receptor blockade, prolongs refractoriness (decreased cell excitability) through potassium and sodium blockade, and slows intracardiac conduction through sodium channel blockade.

Cordarone is approved for use in the secondary prevention of life-threatening ventricular arrhythmias in survivors of prolonged ventricular tachyarrhythmias, especially for people with left ventricular dysfunction.

Results from studies using Cordarone for the primary prevention of sudden death in high-risk patients have produced mixed results. The benefit of Cordarone therapy is more pronounced in patients with congestive heart failure.

Cordarone is used to treat atrial fibrillation.

Various practice guidelines recommend Cordarone as a second-line treatment for the long-term treatment of atrial fibrillation with structural heart failure and in highly symptomatic patients without heart failure.

Several studies have shown that Cordarone is similar to Quinidine and Sotalol in the treatment of atrial fibrillation.

Recent studies suggest that aggressive attempts to maintain sinus rhythm using Cordarone or other drugs do not improve outcomes in patients with relatively asymptomatic cases. Therefore, long-term therapy with Cordarone, with its potential toxicity, does not seem justified.

The most serious potential side effect of Cordarone therapy is pulmonary toxicity. The most common clinical manifestation of the drug is subacute cough and progressive shortness of breath.

Instructions for use

Cordarone is recommended for the treatment in secondary prevention of only vital, life-threatening ventricular arrhythmias, and only in selected cases for the treatment of atrial fibrillation.

When taking Cordarone, laboratory tests to assess liver and thyroid function should be performed at least once every six months.

It is advisable to maintain the dosage of Cordarone at the lowest effective level.

In patients taking Digoxin and Warfarin, the physician should pay close attention to Digoxin levels and evaluation of the extrinsic coagulation pathway, keeping in mind that the effects of the interaction with Amiodarone do not peak until seven weeks after initiation of concomitant therapy.

Price

Cost of the drug:

Ekaterinburg, Cordarone, 200 mg, 30 pcs. – 290 rub.
Moscow, Cordarone, 200 mg, 30 pcs. – 338 rub.
Novosibirsk, Cordarone, 200 mg, 30 pcs. – 290 rub.

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Analogues

The following drugs are analogues of Cordarone tablets:

Amiodarone;
Cardiodarone;
Rhythmorest.

Of the antiarrhythmic drugs currently used, amiodarone is one of the most effective drugs with a low risk of proarrhythmia, probably due to their multiple pharmacological effects on cardiac ion channels and receptors.

Proarrhythmia is an intensification of an existing arrhythmia or the emergence of a new one under the influence of antiarrhythmic drugs.

Reviews

Evgeniy, arrhythmia. I was in the hospital and they prescribed this drug to improve my heart rhythm.

Apparently, I am allergic to it, because within a few minutes after the IV started working, I got a feeling of heat, as if CT contrast dye had been injected into my blood.

Of course, I was taken off the IV straight away and there don't seem to be any long term problems since I was only on the IV for a short time.

Olga. Ventricular arrhythmia. My 73 year old mother was prescribed this drug after bypass surgery. She went through surgery but experienced side effects from the drug. Her kidneys, liver and lungs reacted and she was unable to overcome the side effects of this drug. I would like to point out that she never smoked or drank alcohol.

Oleg. Ventricular arrhythmia. Took the drug, heart rate was stable for three weeks, and was discharged from the hospital. The potential side effects are scarring on the lungs, liver and thyroid, which I think I'm already developing, it's very scary. I would like to no longer take this drug.

Andrey. Arrhythmia. My father died as a result of taking this drug, he was not warned about the possible pulmonary toxicity that killed him. When the symptoms became obvious, I took him to the doctor. Doctors prescribed antibiotics thinking that my father had a cold. He ended up in intensive care with pneumonia. It took almost two days to determine the cause - Cordarone. After 62 days in the intensive care unit, my father passed away. It's amazing how many people experience the same terrible result. Avoid this medication unless needed as a last resort!

Oleg. Ventricular tachycardia. Six months after the bypass was performed, I had a defibrillator implanted. Over four years, a slow but steady increase in short heart rhythms appeared. Cordarone 200 mg twice daily was prescribed, and after the increasing rhythms stabilized, the dose was reduced to 200 mg once daily. Over the next 2 years, the heart rhythms and their severity decreased dramatically, and now there are practically no problems with heart rhythms. There are mild side effects including constipation, skin tingling, short-term memory loss and occasional episodes of motor instability.

Cordarone is considered one of the most effective antiarrhythmic drugs, but also one of the most toxic. Generally, Cordarone is considered a drug of last resort that should only be used for a short period of time.

Before taking Cordarone, it is important to carefully check all organ systems (especially the lungs), and keep copies of any tests. This will allow you to monitor the normal level of functioning of the body and how quickly adverse changes develop in order to adjust the intake.

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Dosage form: tablets Composition:

One tablet contains:

active substance - amiodarone hydrochloride 200.0 mg;

Excipients: lactose monohydrate, corn starch, magnesium stearate, povidone K 90 F anhydrous colloidal silicon dioxide.

Description: White to off-white round tablets with a break line on one side and a bevel 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. Pharmacotherapeutic group:antiarrhythmic agent ATX:

C.01.B.D.01 Amiodarone

Pharmacodynamics:

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

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 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 atrioventricular 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 atrioventricular node;

slowing down conduction and increasing the duration of the refractory period in additional atrioventricular conduction bundles.

Other effects:

lack of negative inotropic effect when taken orally; reduction of myocardial oxygen consumption due to a moderate decrease in peripheral resistance and heart rate; 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 metabolism 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.

Therapeutic effects are observed on average a week after starting to take the drug (from several days to two weeks). After stopping its use, it is determined 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 varies from 30 to 80% in different patients (average value about 50%). After a single oral dose of amiodarone, maximum plasma concentrations are reached within 3-7 hours. However, the therapeutic effect usually develops a week after starting the drug (from several days to two weeks). is a drug with a slow release into tissues and high affinity for them.

The connection with blood plasma proteins is 95% (62% with albumin, 33.5% with beta-lipoproteins). has a large volume of distribution. During the first days of treatment, the drug accumulates in almost all tissues, especially in adipose tissue and, in addition to it, in the liver, lungs, spleen and cornea.

Amiodarone is metabolized in the liver via isoenzymes CYP3A4 and CYP2C8. Its main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. and its active metabolite desethylamiodarone in vitro have the ability to inhibit isoenzymes CYP 1 A 1, CYP 1 A 2, CYP 2 C 9, CYP 2 C 19, CYP 2 D 6, CYP 3 A 4, CYP 2 A 6, CYP 2 B 6 and CYP 2 C 8. 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 the achievement of 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. and its metabolites are not excreted by hemodialysis. has a long half-life with large 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: the initial half-life (first phase) is 4-21 hours, the half-life in the 2nd phase is 25-110 days. After prolonged oral administration, the average half-life 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 per 24 hours with a daily dose of amiodarone 200 mg). Most of the iodine remaining in the drug is excreted through the intestines after passing through the liver, however, with prolonged use of amiodarone, iodine concentrations in the blood can reach 60-80% of amiodarone concentrations in the blood. The peculiarities of the pharmacokinetics of the drug explain the use of “loading” doses, which are aimed at the rapid accumulation of amiodarone in tissues, 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.

Indications:

Life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be started in the hospital with careful cardiac monitoring).

Supraventricular paroxysmal tachycardias:

documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with organic heart disease;

documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients without organic heart disease, when antiarrhythmic drugs of other classes are not effective or there are contraindications to their use;

documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome.

Atrial fibrillation (atrial fibrillation) and atrial flutter Prevention of sudden arrhythmic death in high-risk patients

- Patients after a recent myocardial infarction with more than 10 ventricular extrasystoles per hour, clinical manifestations of chronic heart failure and a reduced left ventricular ejection fraction (less than 40%).

Cordarone® can be used in the treatment of rhythm disturbances in patients with coronary heart disease and/or impaired left ventricular function. Contraindications:

Hypersensitivity to iodine, amiodarone or excipients of the drug.

Galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose).

Sick sinus syndrome, sinus bradycardia, sinoatrial block in the absence of an installed artificial pacemaker (pacemaker) in the patient (risk of “stopping” the sinus node).

Atrioventricular block II-III degree, in the absence of an installed artificial pacemaker (pacemaker) in the patient.

Hypokalemia, hypomagnesemia.

Combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including ventricular torsade de pointes (see section "Interaction with other drugs"):

Antiarrhythmic drugs: class IA (hydroquinidine, disopyramide); antiarrhythmic drugs III class (dofetilide, ibutilide, ); ; other (non-antiarrhythmic) drugs such as bepridil; ; some neuroleptics: phenothiazines (cyamemazine), benzamides (sultopride, sulpride, veralipride), butyrophenoids (.), pimozide; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular when administered intravenously); azoles; antimalarials (quinine, halofantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; , terfenadine; fluoroquinolones.

Congenital or acquired prolongation of the QT interval.

Thyroid dysfunction (hypothyroidism, hyperthyroidism).

Interstitial lung disease.

Pregnancy (except in special cases, see section "Use during pregnancy and lactation").

Lactation period (see section "Use during pregnancy and lactation").

Age up to 18 years (efficacy and safety have not been established).

Carefully:

For decompensated or severe chronic(III - IV FC according to classification NYHA) heart failure, liver failure, bronchial asthma, severe respiratory failure, in elderly patients (high risk of developing severe bradycardia), with first degree atrioventricular block.

Pregnancy and lactation:

Since the fetal thyroid gland begins to bind only from the 14th week of pregnancy (amenorrhea), amiodarone is not expected to affect it 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 thyroid gland of the fetus, it is contraindicated during pregnancy, with the exception of special cases when the expected benefit outweighs the risks (in case of life-threatening ventricular arrhythmias).

Breastfeeding 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).

Directions for use and dosage:

The drug should be taken only as prescribed by a doctor!

Cordarone® tablets are taken orally before meals and washed down with a sufficient amount of water.

Loading ("saturating") dose : Various saturation schemes can be applied.

In the 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 within 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 within 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 effect.

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

Average therapeutic single dose 200 mg.

Average therapeutic daily dose - 400 mg.

Maximum single dose - 400 mg.

Maximum daily dose - 1200 mg.

Side effects:

The frequency of side effects was determined according to the World Health Organization (WHO) classification: very common (>10%); often (> 1%,<10%); нечасто (>0.1 %, < 1 %); редко (> 0,01 %, < 0,1 %) и очень редко, включая отдельные сообщения (<0,01 %); частота неизвестна (по имеющимся данным частоту определить не представляется возможным).

Blood and lymphatic system disorders: 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) (see section "Interaction with other drugs and "). 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 (see section "Interaction with other drugs", subsection "Pharmacodynamic interaction" and section "Special instructions").

Endocrine system disorders: Common - Hypothyroidism. Hyperthyroidism, sometimes fatal. Very rare - Syndrome of impaired secretion of antidiuretic hormone.

Visual disorders: 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 rarely - neuropathy/optic neuritis, which can progress to blindness.

Digestive system disorders:Very common - Nausea, vomiting, dysgeusia (dullness or loss of taste), usually occurring when taking a loading dose and disappearing after a dose reduction. Frequency unknown - Pancreatitis/acute pancreatitis, dry mouth, constipation.

General disorders: Frequency unknown - Formation of granulomas, including bone marrow granuloma.

Disorders of the liver and biliary tract: Very often - An isolated increase in transaminase activity in the blood serum, usually moderate (exceeding the upper limit of normal from 1.5 to 3 times), observed at the beginning of treatment. The activity of “liver” transaminases may return to normal values when the dose is reduced or even spontaneously. Often - Acute liver damage with increased transaminase activity and/or jaundice, including the development of liver failure, sometimes with death (see section "Special Instructions"). 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 rarely - 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 rarely - 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.

Genital and breast disorders: Very rare - Epididymitis, impotence. Frequency unknown - Decreased libido.

Respiratory, thoracic and mediastinal disorders: Common - Pulmonary toxicity(alveolar/and 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 respiratory distress syndrome in adults, sometimes fatal, usually developing immediately after surgery (possible interaction with high concentrations of oxygen) (see sections "Special instructions", "Interaction with other drugs"). Frequency unknown - Pulmonary hemorrhage.

Skin and subcutaneous tissue disorders: 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 rare - Erythema may occur during radiotherapy; skin rash, usually nonspecific, exfoliative dermatitis, alopecia. Frequency unknown - Eczema, urticaria, severe skin reactions, sometimes fatal, including toxic epidermal necrolysis/Stevens-Johnson syndrome, derma bullosa; drug reaction with eosinophilia and systemic symptoms.

Vascular disorders: very rarely - vasculitis.

Overdose:

When ingesting very large doses, several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal ventricular “torsade de pointes” and liver damage have been described. Atrioventricular conduction may slow down and pre-existing heart failure may worsen.

Treatment should be symptomatic (gastric lavage, use 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 ventricular "pirouette" tachycardia - intravenous administration of magnesium salts or cardiac stimulation .

Medicines that slow the heart rate or cause problems with automaticity or conduction

Combination therapy with these drugs is not recommended.

Beta-blockers, blockers of “slow” calcium channels that slow down the heart rate (,) can cause disturbances in automaticity (the development of excessive bradycardia) and conduction.

Medicines that can cause hypokalemia

Not recommended combinations - With laxatives that stimulate intestinal motility, which can cause hypokalemia. increasing the risk of developing ventricular "torsade de pointes" tachycardia. Laxatives from other groups should be used simultaneously with amiodarone.

Combinations requiring caution when using

With diuretics that cause hypokalemia (in monotherapy or in combination with other drugs).

With systemic corticosteroids (glucocorticosteroids, mineralocorticosteroids), tetracosactide.

With amphotericium B (intravenous administration).

It is necessary to prevent the development of hypokalemia, and if it occurs, restore the potassium content in the blood to normal values, monitor the content of electrolytes in the blood and ECG (for possible prolongation of the QT interval). and in the event of ventricular “pirouette” tachycardia, antiarrhythmics should not be used (ventricular cardiac pacing should be started; intravenous administration of magnesium salts is possible). Medicines for general anesthesia

The possibility of developing the following severe complications in patients taking the drug during general anesthesia has been reported: bradycardia (resistant to the administration of atropine), decreased blood pressure, conduction disorders, decreased cardiac output.

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

Medicines that reduce heart rate (, guanfac, cholinesterase inhibitors (, tacrine, ambenonium chloride, neostigmia bromide),)

Risk of developing excessive bradycardia (cumulative effects).

Effect of amiodarone on other drugs

Amiodarone and/or its metabolite desethylamiodarone inhibit the isoenzymes CYP1AI, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-gp and may increase the systemic exposure of drugs that are their substrates. Due to the long half-life of amiodarone, this interaction may occur even several months after discontinuation of use.

Drugs that are P-gp substrates

Amiodarone is a P-gp inhibitor. It is expected that its co-administration with drugs that are P-gp substrates will lead to an increase in the systemic exposure of the latter.

Cardiac glycosides (digitalis preparations)

Dabigatran

Caution should be exercised when using amiodarone and dabigatran concomitantly due to the risk of bleeding. The dose of dabigatran may need to be adjusted in accordance with the instructions in its instructions for use.

Medicines that are substrates of the CYP2C9 isoenzyme

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

Warfarin

When warfarin is combined with amiodarone, the effects of the indirect anticoagulant may be enhanced, which increases the risk of bleeding. The prothrombin time should be monitored more often by determining the INR (international normalized ratio) and dose adjustments of indirect anticoagulants should be made, both during treatment with amiodarone and after stopping it.

Phenytoin

Medicines that are substrates of the CYP2D6 isoenzyme

Flecainide

Amiodarone increases plasma concentrations of flecainide due to inhibition of the CYP2D6 isoenzyme, which requires adjustment of flecainide doses.

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

Cyclosporine

The combination of cyclosporine with amiodarone may increase plasma concentrations of cyclosporine; dose adjustment is necessary.

Fentanyl

Combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects.

HMG-CoA reductase inhibitors (statins) (, and lovastaty)

Increased risk of muscle toxicity (rhabdomyolysis) with concomitant use of amiodarone and statins. metabolized by the CYP3A4 isoenzyme. The use of statins that are not metabolized by the CYP3A4 isoenzyme is recommended.

Other medicinal products metabolized by CYP3A4: (risk of sinus bradycardia and neurological symptoms), (risk of nephrotoxicity), (risk of increased side effects), (risk of psychomotor effects), triazolam. Dihydroergotamine. ergotamine. .

A drug that is a substrate of the CYP2D6 and CYP3A4 isoenzymes.

Dextromethorphan

Amiodarone inhibits CYP2D6 and CYP3A4 isoenzymes and theoretically may increase plasma concentrations of dextromethorphan.

Clopidogrel

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

Effect of other drugs on amiodarone

Inhibitors of CYP3A4 and CYP2C8 isoenzymes may have the potential to inhibit the metabolism of amiodarone, increasing its concentration in the blood and, accordingly, the risk of increasing its pharmacodynamic and side effects.

It is recommended to avoid taking inhibitors of the CYP3A4 isoenzyme (for example, grapefruit juice and certain drugs, such as HIV protease inhibitors (including) during treatment with amiodarone. HIV protease inhibitors, when used simultaneously with amiodarone, may increase the concentration of amiodarone in the blood.Inducers of the isoenzyme CYP3A4

Rifampicin

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

Preparations of St. John's wort

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

Special instructions:

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. Patients should be warned to avoid exposure to direct sunlight or to take protective measures (eg, use of sunscreen, wearing appropriate clothing) during treatment. Reactions from the heart 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 Q-Tc interval by no more than 450 ms or by no more than 25% of the original value.

In elderly patients, a significant slowdown in heart rate may occur. With the development of atrioventricular block II and III degree, sinoatrial block or double-bundle intraventricular block, treatment with Cordarone® should be discontinued. If first degree atrioventricular block occurs, monitoring should be intensified.

The occurrence of new rhythm disturbances or worsening of existing rhythm disturbances, sometimes with a legal outcome, has been reported. It is very important, but difficult, to make a differential diagnosis between the insufficient effectiveness of the drug and its arrhythmogenic effect, whether or not combined with an aggravation of the severity of cardiovascular pathology. When using the drug Cordarone®, arrhythmogenic effects were reported significantly less frequently than with other antiarrhythmic drugs and, as a rule, it was observed in the presence of factors that increase the duration of the QT interval, such as interactions with other drugs and / or disturbances in the content of electrolytes in the blood (see sections "Side effects" and "Interaction with other drugs"). Despite the ability of the drug Cordarone® to increase the duration of the QT interval, it showed low activity in relation to the provocation of ventricular "torsade de pointes" tachycardia.

Hyperthyroidism (see section "Side effects"). While taking the drug Cordarone® or for several months after stopping it, hyperthyroidism may develop. Clinical manifestations are usually mild, so symptoms such as weight loss, the occurrence of rhythm disturbances, angina attacks, and the development of chronic heart failure should alert the doctor. The diagnosis is confirmed by identifying a decrease in the concentration of TSH in the blood serum, determined using an ultrasensitive TSH test. In this case, taking Cordarone® should be discontinued. Recovery usually occurs within several months after discontinuation of treatment: first, the disappearance of clinical manifestations is observed, and then normalization of laboratory parameters of thyroid function occurs. Severe cases of thyrotoxicosis, which can sometimes be fatal (both due to 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.

Neuromuscular disorders (see section "Side effects")

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.

Visual disorders

If vision is blurred or visual acuity decreases, a complete ophthalmological examination, including examination of the fundus of the eye (funduscopy), is urgently necessary. If neuropathy and/or optic neuritis is detected, Cordarone® should be discontinued due to the risk of their progression to the development of blindness.

Pulmonary disorders

The appearance of shortness of breath or dry cough may be associated with pulmonary toxicity, in particular the development of interstitial pneumonitis. If the development of interstitial pneumonitis is suspected in patients who experience severe shortness of breath, either isolated or in combination with a deterioration in general condition (fatigue, weight loss, fever), an X-ray examination of the lungs should be performed. The need to use Cordarone® should be re-evaluated, since if it is discontinued early, interstitial pneumonitis is usually reversible (clinical symptoms usually resolve within 3-4 weeks, followed by a slower improvement in radiographic appearance and pulmonary function 15 over several months). Treatment with glucocorticosteroids should be considered.

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

Liver disorders

Careful monitoring of liver function tests (monitoring the activity of liver transaminases) is recommended before starting use of the drug Cordarone® and regularly during treatment with the drug. When taking Cordarone®, acute liver dysfunction (including hepatocellular failure or liver failure, sometimes fatal) and chronic liver damage are possible. Therefore, if the activity of “liver” transaminases increases, 3 times higher than the upper limit of normal, the dose of the drug Cordarone® should be reduced or discontinued. Clinical and laboratory signs of chronic liver failure when using the drug Cordarone® orally can be minimally expressed (hepatomegaly, increased transaminase activity, 5 times the upper limit of normal) and reversible after discontinuation of the drug, but cases of death have been reported.

Severe bullous reactions

You should immediately stop treatment with Cordarone® if symptoms and manifestations of life-threatening or even fatal reactions appear in the form of Steven-Johnson syndrome, toxic epidermal necrolysis, namely the appearance of a progressive skin rash, often with the formation of blisters, or damage to the mucous membranes.

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 (,); laxatives that stimulate intestinal motility, which can cause hypokalemia.

Treatment monitoring

Before starting to take the drug Cordarone®, it is recommended to conduct an ECG study and determine the potassium content in the blood serum. Hypokalemia must be corrected before using Cordarone®. During treatment, it is necessary to regularly monitor the ECG, as well as the activity of liver transaminases and other indicators of liver function.

In addition, due to the fact that the drug Cordarone® can cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid diseases, before taking the drug Cordarone®, a clinical and laboratory examination should be carried out to identify dysfunction of the thyroid gland (TSH concentration in serum, determined using an ultrasensitive TSH test). During treatment with Cordarone® and for several months after its cessation, the patient should be regularly examined to identify clinical or laboratory signs of changes in thyroid function. If thyroid dysfunction is suspected, it is necessary to determine the concentration of TSH in the blood serum (using an ultrasensitive TSH test).

Increased rates of ventricular defibrillation and/or increased thresholds for pacemaker or implanted defibrillator response have been reported in patients receiving antiarrhythmic drugs over a long period of time, which may reduce the effectiveness of these devices. Therefore, before starting or during treatment with Cordarone®, you should regularly check their correct functioning.

Regardless of the presence or absence of pulmonary symptoms during treatment with Cordarone®, it is recommended to conduct an X-ray examination of the lungs and pulmonary function tests every 6 months. Deviations from the norm in the concentration of thyroid hormones. Since the drug Cordarone® contains, its use may interfere with the absorption of radioactive iodine and distort the results of a radioisotope study of the thyroid gland, however, taking the drug does not affect the reliability of determining the concentration of free T3, T4, TSH (using an ultrasensitive method for determining the concentration of TSH) in the blood serum.

The drug Cordarone® inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (an increase in the concentration of free T4 in the blood serum, with a slightly reduced or even normal concentration of free T3 in the serum) in clinically euthyroid patients, which is not is a reason to discontinue the drug Cordarone®.

The development of hypothyroidism can be suspected when the following clinical signs, usually mild, appear: weight gain, cold intolerance, decreased activity, severe bradycardia (see section "Side effects"). The diagnosis is confirmed by a clear increase in the concentration of TSH in the blood serum, determined using an ultrasensitive method for determining the concentration of TSH.

Normalization of thyroid function is usually observed within 1-3 months after cessation of treatment. In life-threatening situations, treatment with Cordarone® can be continued with simultaneous additional use of L-thyroxine under the control of TSH concentration in the blood serum.

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).

Impact on the ability to drive vehicles. Wed and fur.:

Based on safety data, there is no evidence that it impairs the ability to drive vehicles or engage in other potentially hazardous activities. However, as a precautionIt is advisable for patients with paroxysms of severe rhythm disturbances during treatment with Cordarone® to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Release form/dosage:

Tablets 200 mg.

Package: 10 tablets per PVC/Al blister. 3 blisters along with instructions for use in a cardboard box. Storage conditions:

Store at a temperature not exceeding 30°C.

Keep out of the reach of children.

Best before date:

3 years.

Do not use the drug after the expiration date indicated on the package.

Conditions for dispensing from pharmacies: On prescription Registration number: P N014833/02 Registration date: 27.01.2009 Owner of the Registration Certificate:Sanofi-Aventis France France Manufacturer: Representative office: Sanofi Russia, JSC Russia Information update date: 13.04.2015 Illustrated instructions

Cordarone is an antiarrhythmic drug whose main active ingredient is amiodarone hydrochloride.

The drug is available in the form of a solution for intravenous injection and in tablet form. The active substance has coronary dilation, antianginal, hypotensive, alpha-adrenergic blocking, beta-adrenergic blocking effects.

In this article we will look at why doctors prescribe Cordarone, including instructions for use, analogues and prices for this drug in pharmacies. Real REVIEWS of people who have already used Cordarone can be read in the comments.

Composition and release form

Available in tablet form with a standard dosage of 200 mg. Distinctive features - on each tablet there is a symbol of the myocardium and the amount of active substance. Based on these factors, counterfeit analogues can be identified.

The main active ingredient is amiodarone hydrochloride.

Clinical and pharmacological group: antiarrhythmic drug.

Indications for use

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

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

Cordarone is also used to prevent relapses:

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

pharmachologic effect

Cordarone is a third class antiarrhythmic drug. Eliminates angina pectoris and arrhythmia, helps block adrenergic receptors, slow down sinoatrial, atrial and nodal conduction, without affecting intraventricular conduction.

The mechanism of pharmacological action is divided into several components:

normalization of heart rate;
increasing the energy potential of cardiac muscle cells;
increase in AV conduction in comparison with ventricular processes;
regulation of refractory processes with periodic contraction of the atria and ventricles of the heart muscle;
blocking the conduction of electrical impulses through potassium channels;
reducing the level of influence of automatic regulation of impulse processes originating from the sinus node of the heart muscle;
regulation of cardiac output volume and stabilization of the pulse wave.

To obtain a lasting therapeutic effect, the drug must be taken for at least 10 days.

Instructions for use

According to the instructions for use, Cordarone tablets are taken orally, before meals, with a small amount of water. The dosage is prescribed by the doctor based on clinical indications and the patient’s condition.

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

In the hospital: the initial dose, divided into several doses, ranges from 600-800 mg (up to a maximum of 1200 mg) / day until a total dose of 10 g is reached (usually within 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 within 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 effect.

Because Cordarone has a very large T1/2, it can be taken every other day or take breaks from taking it 2 days a week.

Contraindications

The drug should not be used in the following cases:

Hypersensitivity to Cordarone or its components;
Use of Cordarone in any trimester of pregnancy;
Increased concentration of potassium ions in the blood;
Sick sinus node syndrome of the cardiac conduction system;
Increased concentration of magnesium ions in the blood;
Violation of the functional activity of the thyroid gland;
Individual intolerance to Cordarone or its components;
Congenital prolongation of the QT interval;
Use of Cordarone during breastfeeding;
Acquired prolongation of the QT interval;
Mixing Cordarone in one syringe with other medications.

The simultaneous use of Cordarone with Quinidine, Disopyramide, Trifluoperazine, Amisulpride, Sulpiride, Veraliprid, Droperidol, Haloperidol, Pimozide, Sertindole, Dofetilide, Bretylium Tosylate, Vincamine, Cyamemosine, Thioridazine, Fluphenazine, Levomepromazine, Cisapride, antidepressant drugs is prohibited. cyclic series, Spiramycin, Chlorochone , Sultopride, Erythromycin, azole group drugs, Chloroquine, Halofantrine, Difemanil methyl sulfate, Astemizole, fluoroquinolone group drugs, Hydroquinidine, Procainamide, Ibutilide, Sotalol, Bepridil, Chlorpromazine, Mefloquine, Pentamidine, Mizolastine and Terfenadine.

Side effects

When using the drug Cordarone, undesirable effects are possible in the form of:

Nausea;
Tremors;
Pulmonitis;
Alveolitis;
Lipofuscin deposits in the corneal epithelium;
Photosensitivity;
Bradycardia;
Arterial hypotension;
Slowing of AV conduction;
Liver dysfunction;
Peripheral neuropathy.
With long-term therapy or use in high doses: development of hypothyroidism, hyperthyroidism.

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

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

Cordarone's analogs

Structural analogues of the active substance:

Amiodarone;
Amiocordin;
Vero Amiodarone;
Cardiodarone;
Opacordan;
Rhythmiodarone;
Sedakoron.

Attention: the use of analogues must be agreed with the attending physician.

Price

The average price of CORDARONE in pharmacies (Moscow) is 310 rubles.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Zina
I was prescribed the use of cordarone according to the following scheme: 3 days, 2 tablets three times a day, 3 days, 1 tablet 3 times a day, 3 days, 1 tablet 2 times a day, then 1 tablet a day until the end of the package. I had to be protected from heart failure for at least 6 months. Alas... 3 days after stopping taking cordarone tablets, everything resumed, albeit in a weakened feeling. I save myself by taking 1/2 tablets per day of Coronal. We need to go to the cardiologist again (((
Valentin Semenovich
I am 76 years old. Rhythm disturbances since the age of 30. The number of systoles per minute was 30 with a pulse of 60 beats per minute. I tried different drugs - it was useless (perhaps there were no effective drugs at that time). During a consultation at the cardiology center, a diagnosis of ventricular extrasystole was made and cordarone was recommended. I have been taking it for more than 40 years, 100-200 mg per day in the morning. Side effects include:
– periodic decrease in heart rate (mainly in the morning) to no more than 50 beats/min. On average, the pulse is 60-65 beats/min;
– slight increase in the size of the thyroid gland.
Against the background of cordarone (dose no more than 200 mg/day), individual systoles are observed (2-3 systoles per minute); Rarely do group or even double systoles slip through. In one of the anamnesis during the operation (and even then cardiologists question this), atrial fibrillation without paroxysms was recorded. Now the cardiologist recommends changing the drug. But I'm afraid (the best is the enemy of the good). The general opinion about the drug is clearly positive.
Anonymous
I take cordarone 2 ngedel. 1 tablet at a dose of 200 mg. The condition is terrible: nausea, loss of appetite, some attacks of weakness. In a word, I refused, I’m going to the doctor tomorrow.