Cordarone ampoules. Amiodarone (solution, tablets) prescription in Latin and application regimens
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 antiarrhythmic action, because in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (sodium channel blockade), class IV antiarrhythmics (calcium channel blockade) and a non-competitive beta-blocker effect.
In addition to the antiarrhythmic effect, it has antianginal, coronary dilation, alpha and beta adrenergic blocking effects.
Antiarrhythmic properties:
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);
Decreased automatism of the sinus node, leading to a decrease in heart rate;
Non-competitive blockade of alpha and beta adrenergic receptors;
Slowing of sinoatrial, atrial and AV conduction, more pronounced with tachycardia;
No changes in ventricular 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 action when taken orally and parenterally;
Reducing myocardial oxygen consumption due to a moderate decrease in peripheral resistance and heart rate, as well as myocardial contractility due to beta-adrenergic blocking action;
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.
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 sick. The main route of elimination of amiodarone is the intestine. Amiodarone and its metabolites are not eliminated by hemodialysis. Amiodarone has a long T1/2 with great individual variability (therefore, when selecting a dose, for example increasing or decreasing it, it should be remembered that at least 1 month is needed to stabilize the new plasma concentration of amiodarone). Elimination when taken orally occurs in 2 phases: initial T1/2 (first phase) - 4-21 hours, T1/2 in the 2nd phase - 25-110 days (20-100 days). After prolonged oral administration, the average T1/2 is 40 days. After discontinuation of the drug, complete elimination of amiodarone from the body may continue for several months.
Each dose of amiodarone (200 mg) contains 75 mg of iodine. Part of the iodine is released from the drug and is found in the urine in the form of iodide (6 mg/day at daily dose amiodarone 200 mg). Most of the iodine remaining in 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 tachycardias: documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with organic heart diseases; 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 high-risk patients: after a recent myocardial infarction, with more than 10 ventricular extrasystoles in 1 hour, clinical manifestations chronic heart failure and reduced left ventricular ejection fraction (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 a high frequency of ventricular contractions, especially against the background of Wolff-Parkinson-White syndrome; relief of paroxysmal and stable forms of atrial fibrillation (atrial fibrillation) and atrial flutter;
Cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to defibrillation.
Contraindications
Common to both dosage forms
hypersensitivity to iodine, amiodarone or excipients 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); antiarrhythmic drugs Class III (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 the injection form additionally:
intraventricular conduction disorders (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 worse).
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 apply when 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 development of severe bradycardia), with 1st degree AV block.
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, 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 V 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 the 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 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 side of 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). 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 side of the central nervous system: very rarely - benign intracranial hypertension (pseudotumor cerebri), headache.
Immune system disorders: very rarely - anaphylactic shock. Unknown frequency: angioedema.
Reactions at the injection site: often - inflammatory reactions, such as superficial phlebitis, when administered directly into a peripheral vein. Reactions at the injection site, such as: pain, erythema, swelling, necrosis, extravasation, infiltration, inflammation, induration, thrombophlebitis, phlebitis, cellulitis, infection, pigmentation.
Interaction
Drugs that can cause torsade de pointes (TdP) 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 disturbances
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 a normal level, 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 may 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 ®, you should use only a 5% dextrose (glucose) solution. Due to the characteristics of the dosage form of the drug, it is not recommended to use concentrations of the infusion solution less than those obtained by diluting 2 ampoules in 500 ml of 5% dextrose (glucose).
To avoid injection site reactions, amiodarone should be administered through a central venous catheter, except in cases of cardiac resuscitation for ventricular fibrillation refractory to cardioversion, when, in the absence of central venous access, peripheral veins (the largest peripheral vein with maximum blood flow) can be used to administer the drug ) (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 using an electronic pump whenever possible over 20-120 minutes. It can be administered repeatedly 2-3 times within 24 hours. The rate of administration of the drug is adjusted depending on the clinical effect. The therapeutic effect appears within the first minutes of administration and gradually decreases after stopping the infusion, therefore, if it is necessary to continue treatment with injectable Cordarone ®, it is recommended to switch to constant intravenous drip administration of the drug.
Maintenance doses: 10-20 mg/kg/day (usually 600-800 mg, but can be increased to 1200 mg/day) in 250 ml of 5% dextrose (glucose) solution for several days. From the first day of infusion, a gradual transition to taking Cordarone ® orally should begin (3 tablets, 200 mg per day). The dose can be increased to 4 or even 5 tablets. 200 mg per day.
Cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to cardioversion
Intravenous 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, use of 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.
very rarely - vasculitis, epididymitis, several cases of impotence (no relationship with the drug has been established), thrombocytopenia, hemolytic anemia, aplastic anemia.
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 defibrillation-resistant ventricular fibrillation, IV bolus administration of amiodarone should be administered over 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 developing interstitial pneumonitis when severe shortness of breath or a 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 assumed) (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 death. 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, Veresgyház, 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 packaging.
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 fibrillation | |
| 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 |
Instructions for medical use
medicine
Cordarone ®
Tradename
Cordarone ®
International nonproprietary name
Amiodarone
Dosage form
Solution for intravenous injection 150 mg/3 ml
Compound
3 ml of solution contain
active substance amiodarone hydrochloride 150 mg,
Excipients: benzyl alcohol, polysorbate 80, water for injection.
Description
Transparent liquid of pale yellow color.
Farmacotherapy group
Drugs for the treatment of heart diseases.
Class III antiarrhythmic drugs
ATS code C01BD01
Pharmacological properties
Pharmacokinetics
Amiodarone is highly protein bound and typically has a plasma half-life of approximately 50 days. However, there may be significant interindividual variability; There have been reports of half-lives of less than 20 days in some patients and more than 100 days in others. Initial administration of high doses of Cordarone, for example, 600 mg/day, is necessary to more quickly achieve sufficient levels in tissues. Due to the long half-life of the drug, a maintenance dose of 200 mg/day or less is usually necessary. Sufficient time is required to achieve a new level of uniform distribution when adjusting the dose. The long half-life is important from a safety point of view for patients with potentially fatal arrhythmias, as inadvertently missing doses has little effect. The content of administered amiodarone quickly decreases in the blood, as tissue saturation is achieved and the drug enters the receptor zones. The effects reach their maximum after approximately 15 minutes and subside within 4 hours. There are no controlled studies in pediatrics. In the limited published data available, no differences have been noted in the pediatric population compared to adults.
Pharmacodynamics
Antiarrhythmic propertiesCordarona:
Prolongation of the 3rd phase of cardiac activity potential without affecting its height or rate of rise (Vaughan Williams class III). Isolated prolongation of the 3rd phase of the activity potential is due to a slowdown in the activity of potassium channels, while no changes in the function of sodium or calcium channels occur
Bradycardizing effect as a result of decreased automatism of the sinus node. This effect is not reversed by atropine.
Non-competitive alpha and beta antiadrenergic effect
Slow sinoatrial, atrial (atrial) and nodal conduction, which is more pronounced the faster the rhythm.
No change in ventricular conduction
Increased refractory periods and decreased myocardial excitability at the atrial, nodal and ventricular levels
Slowing of conduction and prolongation of refractory periods in the atrioventricular accessory pathways
No negative inotropic effects.
Indications for use
Severe arrhythmias, in case of inappropriate treatment by oral route:
Atrial arrhythmia with rapid ventricular rate
Tachycardia in Wolff-Parkinson-White syndrome
Documented symptomatic and
disabling ventricular arrhythmia
Cardiopulmonary resuscitation in case of cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy.
Directions for use and doses
For intravenous administration, concentrations less than 2 ampoules per 500 ml should not be used. Only isotonic glucose solution should be used. Do not add other drugs to the prepared infusion solution.
Cordarone ® should be administered through central venous access, with the exception of cardiopulmonary resuscitation in the case of cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy: in such cases, in the absence of central venous access, peripheral venous access can be used (see "Special precautions and special precautions"). precautions for use").
Severe arrhythmias when oral treatment is not suitable, with the exception of cardiopulmonary resuscitation in the event of cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy.
Infusion via central venous access
- initial treatment: On average, 5 mg/kg in glucose solution is administered over 20 minutes to 2 hours, can be repeated 2-3 times over a 24-hour period. The short duration of action of the drug requires continuous infusion.
- maintenance treatment: 10-20 mg/kg/day (average 600-800 mg/24 hours, up to 1.2 g/24 hours) in 250 ml glucose solution, for several days. The transition to oral treatment (3 tablets per day) begins on the first day of infusion. This dose can be increased to 4 or even 5 tablets per day.
Cardiopulmonary resuscitation in case of cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy.
Regarding the route of administration, and taking into account the situation to which this indication relates, the use of a central venous catheter is recommended if it is readily available; otherwise, the drug can be administered through a peripheral venous approach, using the largest peripheral vein with the strongest blood flow.
The initial intravenous dose is 300 mg (or 5 mg/kg), diluted in 20 ml of 5% glucose solution, administered quickly.
An additional intravenous dose of 150 mg (or 2.5 mg/kg) is possible if ventricular fibrillation persists.
Do not add any other medications to the syringe.
Side effects
very often (³ 10%), often (³ 1% -< 10%), нечасто (³ 0,1% - < 1%), редко (³ 0,01% - < 0,1%), очень редко (< 0,01%).
Often
Nausea
Often
- bradycardia
- inflammatory reaction such as superficial phlebitis when administered directly through peripheral venous access, injection site reactions (pain, erythema, swelling, necrosis, extravasation, infiltration, inflammation, thrombophlebitis and cellulitis)
Usually, a moderate and transient decrease in blood pressure. Cases of severe hypotension and vascular insufficiency, in particular after overdose or after too rapid administration.
Very rarely
Severe bradycardia and, even less frequently, sinus node arrest, especially in elderly patients
Proarrhythmic effect
Liver lesions diagnosed based on increased transaminase activity:
Moderate and isolated increase in transaminase levels (1.5 - 3 times higher than normal) and their decrease after dose reduction or even spontaneously
Acute liver damage with increased levels of transaminases in the blood and/or jaundice (sometimes fatal), requiring discontinuation of treatment
Chronic liver damage during long-term treatment (orally). Histology is consistent with pseudoalcoholic hepatitis. Since laboratory signs are uncertain (intermittent hepatomegaly, increased blood transaminases 1.5 - 5 times higher than normal), regular monitoring of liver function is justified. Chronic liver damage should be suspected even in the case of a moderate increase in blood transaminases observed after treatment lasting more than 6 months. Clinical and biological changes usually regress after treatment is discontinued. Several cases of irreversible changes have been reported.
- anaphylactic shock
- benign intracranial hypertension (pseudotumor cerebri)
Acute respiratory distress syndrome, usually associated with interstitial pneumopathy, in some cases fatal, sometimes immediately after surgery (possible interaction with high doses of oxygen).
Discontinuation of Cordarone should be considered and the feasibility of treatment with corticosteroids should be explored.
Bronchospasm and/or apnea in cases of severe respiratory failure, in particular in patients with asthma
- increased sweating, hair loss
- tides.
Contraindications
Sinus bradycardia or sinoatrial block in patients without a pacemaker
Sick sinus syndrome in patients without a pacemaker (risk of sinus arrest)
High degree of atrioventricular conduction impairment in patients without an artificial pacemaker
Hyperthyroidism due to possible exacerbation provoked by Cordarone
Known hypersensitivity to iodine, amiodarone or any of the excipients
Circulatory collapse
Severe hypotension
Children under 3 years of age due to the presence of benzyl alcohol
Pregnancy and lactation
Combination with drugs that can cause torsade de pointes:
- Class Ia antiarrhythmics(quinidine, hydroquinidine,
disopyramide)
- Class III antiarrhythmics(sotalol, dofetilide, ibutilide)
- other drugs, such as bepridil, cisapride,
difemanil, erythromycin IV, mizolastine, moxifloxacin, spiramycin
IV, IV vincamine (see “Drug Interactions”)
- sultopride
These contraindications do not apply to the use of Cordarone for cardiopulmonary resuscitation in cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy.
Drug interactions
Medicines that can cause torsade de pointes (TdP)
This serious arrhythmia can be caused by a number of drugs, both antiarrhythmic and non-antiarrhythmic. Hypokalemia is a predisposing factor, as is bradycardia or congenital or acquired pre-existing prolongation of the QT interval.
Drugs that can cause torsade de pointes include class Ia antiarrhythmics, class III antiarrhythmics, and some antipsychotics.
Drugs that cause bradycardia
Many drugs can cause bradycardia, including class Ia antiarrhythmics, beta blockers, some class III antiarrhythmics, some calcium channel blockers, digitalis, pilocarpine, and anticholinesterase drugs.
Risk of excessive bradycardia (additive effects).
Contraindicated combinations
Medicines that can cause torsade de pointes:
- class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide)
Class III antiarrhythmics (dofetilide, ibutilide, sotalol)
Other drugs such as bepridil, cisapride, difemanil, erythromycin IV, mizolastine, vincamine IV, moxifloxacin, spiramycin IV
Sulptopride
Increased risk of ventricular arrhythmias, in particular torsade de pointes.
These contraindications do not apply to the use of Cordarone for cardiopulmonary resuscitation in cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy.
Cyclosporine
Increased concentrations of cyclosporine in the blood due to decreased metabolism in the liver, with a risk of nephrotoxic effects.
Analysis of cyclosporine blood concentrations, monitoring of renal function and dosage adjustments during treatment with Cordarone and after cessation of treatment.
Injectable diltiazem
Injectable verapamil
Risk of bradycardia and atrioventricular block. If the use of this combination cannot be avoided, then strict clinical surveillance and continuous ECG monitoring are necessary.
Increased risk of ventricular arrhythmias, in particular torsade de pointes. If possible, azole antifungals should be discontinued. If use of this combination cannot be avoided, prior measurement of the QT interval and ECG monitoring are necessary.
Neuroleptics that can provoke tachycardia type pirouette:
some phenothiazine antipsychotics(chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, tiapride, veralipride), butyrophenones (droperidol, haloperidol) and other antipsychotics (pimozide)
Increased risk of ventricular arrhythmias, in particular torsade de pointes.
Methadone
Increased risk of ventricular arrhythmias, in particular torsade de pointes. Clinical and ECG monitoring.
Combinations requiring precautions during use
Oral anticoagulants
Strengthening the anticoagulant effect and increasing the risk of bleeding due to an increase in the concentration of the anticoagulant in plasma.
More frequent monitoring of prothrombin time and monitoring of international normalized ratio. The dosage of the oral anticoagulant should be adjusted during treatment with Cordarone and after discontinuation of therapy.
Beta blockers other than sotalol (contraindicated combination) and esmolol (combination requiring precautions)
Impaired contractility, automaticity and conduction (compensatory sympathetic mechanisms are suppressed). Clinical and ECG monitoring.
Beta blockers for heart failure (bisoprolol, carvedilol, metoprolol, nebivolol)
Impaired automaticity and cardiac conduction (synergistic effects) with the risk of excessive bradycardia. Increased risk of developing ventricular arrhythmia, in particular tachycardia of the torsade de pointes type. Clinical and regular ECG monitoring.
Digitalis preparations
Suppression of automaticity (excessive bradycardia) and disturbances of atrioventricular conduction. If digoxin is used, the level of digoxin in the blood increases due to reduced clearance of digoxin.
ECG and clinical monitoring, monitoring digoxin blood levels and adjusting digoxin dose if necessary.
Oral diltiazem
Oral verapamil
Risk of developing bradycardia or atrioventricular block, especially in elderly subjects. ECG and clinical monitoring.
Esmolol
Impaired contractility, automaticity and conductivity (compensatory sympathetic mechanisms are suppressed). ECG and clinical monitoring.
Hypokalemic drugs: hypokalemic diuretics (alone or in combination), stimulant laxatives, amphotericin B (IV route), glucocorticoids (systemic administration), tetracosactide.
Increased risk of ventricular arrhythmias, in particular torsades de pointes (hypokalemia is a predisposing factor). ECG, laboratory tests and clinical monitoring.
Lidocaine
The risk of increased lidocaine plasma concentrations with possible neurological and cardiac adverse reactions due to amiodarone reducing its metabolism in the liver. Clinical and ECG monitoring and, if necessary, control of plasma lidocaine concentrations. If necessary, adjust the dosage of lidocaine during treatment with amiodarone and after its discontinuation.
Orlistat
Risk of decreased plasma concentrations of amiodarone and its active metabolites. Clinical monitoring and ECG monitoring if necessary.
Phenytoin (with extrapolation to fosphenytoin)
Increased plasma concentration of phenytoin with signs of overdose, in particular with neurological signs (reduced metabolism of phenytoin in the liver). Clinical monitoring, control of fetinoin plasma concentrations and possible dose adjustment.
Simvastatin
Increased risk of adverse reactions (dose-dependent), such as rhabdomyolysis (decreased hepatic metabolism of cholesterol-lowering drugs). Do not exceed the simvastatin dosage of 20 mg/day.
If the therapeutic goal is not achieved at this dosage, another statin that is not involved in this type of interaction is used.
Tacrolimus
Increased levels of tacrolimus in the blood due to the suppression of its metabolism by amiodarone. Measure tacrolimus blood levels, monitor renal function, and adjust tacrolimus dosage during combination and after discontinuation of Cordarone.
special instructions
Cautionsregarding the route of administration
Infusion via central venous access: severe arrhythmias when oral treatment is unacceptable, with the exception of cardiopulmonary resuscitation for cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy.
Injectable Cordarone ® must be administered through central venous access because administration through peripheral venous access may cause local reactions such as superficial phlebitis. Injectable Cordarone ® should be administered exclusively as an infusion. Even a very slow injection given directly into a vein can worsen hypotension, heart failure and severe respiratory failure (see Side Effects).
Cardiopulmonary resuscitation in case of cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy
Administration via a peripheral vein is generally not recommended due to hemodynamic risk (severe hypotension, vascular insufficiency); the infusion should be administered through a central vein whenever possible
The use of a central venous catheter is recommended if one is immediately available, otherwise the drug can be administered through peripheral venous access, using the largest peripheral vein with the highest blood flow
Monitoring in the intensive care unit with continuous monitoring of blood pressure and ECG should be started as soon as possible
Do not add any other medications to the syringe.
If continuous treatment with Cordarone is required, then it should be administered by infusion and through central venous access with continuous monitoring of blood pressure and ECG.
Cautions, Relatedamiodarone
Cardiac effects
Development of a new arrhythmia and worsening of a pre-existing, treated arrhythmia (see “Side effects”).
The arrhythmogenic effect of amiodarone is weak or even lower than the effect of most antiarrhythmic drugs; it usually occurs with certain drug combinations (see “Drug Interactions”) and with electrolyte imbalance.
Lung symptoms
There are several known cases of interstitial pneumopathy associated with injectable amiodarone. The development of shortness of breath or dry cough, including along with deterioration of the general condition, indicates the possibility of pulmonary toxicity, such as interstitial pneumopathy, and requires radiological examination (see "Side effects").
In addition, several cases of acute respiratory distress syndrome have been observed immediately after surgery in patients treated with amiodarone. In this regard, strict monitoring of such patients is recommended during artificial ventilation.
Liver symptoms
Severe hepatocellular injury, sometimes fatal, may occur within 24 hours of starting treatment with injectable amiodarone (see Side Effects). Regular monitoring of liver function is recommended at the beginning of treatment and then regularly throughout treatment with Cordarone (see “Side effects”).
Special precautions for use
Electrolyte imbalances, in particular hypokalemia: It is important to consider conditions associated with hypokalemia, which may favor the manifestation of a proarrhythmic effect. Hypokalemia should be corrected before administering amiodarone.
Apart from emergency situations, injectable amiodarone should be administered only in a specialized hospital and with continuous monitoring (ECG, blood pressure).
Anesthesia
Before surgery, the anesthesiologist should be informed that the patient is being treated with Cordarone.
Long-term treatment with amiodarone increases the risk of hemodynamic disturbances associated with general and local anesthesia and manifested in the form of adverse reactions. Adverse reactions include, but are not limited to, bradycardia, hypotension, decreased cardiac output, and conduction disturbances.
The combination (see "Drug Interactions") with beta-blockers other than sotalol (contraindicated combination) and esmolol (combination requiring precautions), verapamil and diltiazem is only possible for the prevention of life-threatening ventricular arrhythmias and for Carrying out cardiopulmonary resuscitation in case of cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy.
Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms
Not applicable.
Overdose
Symptoms: There is no information about an overdose of Cordarone by intravenous route. For the oral dosage form, high dose administration at one time is not well documented. Several cases of sinus bradycardia, ventricular arrhythmias, in particular torsade de pointes, and liver damage have been reported.
Treatment: symptomatic. Considering the pharmacokinetic profile of the drug, it is recommended to monitor the patient’s condition for a sufficiently long time, especially his cardiac activity. Amiodarone and its metabolites are not amenable to dialysis.
Release form and packaging
3 ml of solution in colorless glass ampoules in the form of a bottle with a nominal volume of 5 ml with a dot mark for opening.
6 ampoules are placed in a blister pack.
1 blister pack together with instructions for medical use in the state and Russian languages are placed in a cardboard box.
Storage conditions
Store in a dry place, protected from light, at a temperature not exceeding 25 0 C.
Keep out of the reach of children!
Shelf life
Do not use after the expiration date stated on the packaging.
Conditions for dispensing from pharmacies
On prescription
The injection solution is intended for use only in a hospital.
Name and country of the manufacturing organization
Name and country of the marketing authorization holder
Sanofi-aventis France, France
Name and country of the packing organization
Sanofi Winthrop Industries, France
Address of the organization that accepts claims from consumers regarding the quality of products (products) on the territory of the Republic of Kazakhstan
Sanofi-aventis Kazakhstan LLP
050016 Almaty, st. Kunaeva 21B
phone: 8-727-244-50-96
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Dosage form
Solution for intravenous administration 150 mg/3 ml
Compound
3 ml of solution contain
active substance amiodarone hydrochloride 150 mg,
excipients: benzyl alcohol, polysorbate 80, water for injection.
Description
Transparent liquid of pale yellow color, without visible mechanical inclusions.
Pharmacotherapeutic group
Drugs for the treatment of heart diseases. Antiarrhythmic drugs of classes I and III. Class III antiarrhythmic drugs. Amiodarone.
ATX code C01BD01
Pharmacological properties
Pharmacokinetics
As a rule, amiodarone is metabolized by cytochrome CYP3A4 and cytochrome CYP2C8. Amiodarone and its metabolite desethyl-amiodarone are potential in vitro inhibitors of the cytochromes CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and desethyl amiodarone may also inhibit transport proteins such as P-gp and organic cation transporter 2 (OCT2). One study showed a 1.1% increase in creatinine concentration (OCT2 substrate).
Data from in vivo studies demonstrate interactions between amiodarone and CYP3A4, CYP2C9, CYP2D6 and P-gp substrates.
Pediatric patients
There are no controlled studies in pediatrics. In the limited available literature data, no differences in pharmacokinetic parameters were noted in the pediatric population compared to adults.
Pharmacodynamics
Antiarrhythmic properties of Cordarone:
Prolongation of the 3rd phase of cardiac activity potential without affecting its height or rate of rise (Vaughan Williams class III). An isolated prolongation of the 3rd phase of the activity potential is due to a slowdown in the activity of potassium channels, without changes in sodium or calcium channels - the effect of bradycardia as a result of a decrease in the automaticity of the sinus node. This effect is not reversed by atropine.
Non-competitive alpha and beta antiadrenergic effect
Slow sinoatrial, atrial (atrial) and nodal conduction, which is more pronounced the faster the rhythm.
No change in ventricular conduction
Increased refractory periods and decreased myocardial excitability at the atrial, nodal and ventricular levels
Slowing of conduction and prolongation of refractory periods in the accessory atrioventricular pathways
No negative inotropic effects.
Indications for use
Treatment of severe types of arrhythmia in case of impossibility of oral treatment:
Atrial arrhythmia with rapid ventricular rate
Tachyarrhythmia in Wolff-Parkinson-White syndrome
Documented symptomatic and disabling ventricular arrhythmia
Cardiopulmonary resuscitation in case of cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy.
Directions for use and doses
Strictly in a hospital under the supervision of a doctor
For intravenous administration, concentrations of less than 2 ampoules in 500 ml of 5% glucose solution should not be used. Only isotonic glucose solution should be used. Do not add other drugs to the prepared infusion solution.
Cordarone® must be administered through a central vein (central venous access), with the exception of cardiopulmonary resuscitation in the event of cardiac arrest associated with ventricular fibrillation resistant to electrical impulse therapy. In such cases, if administration through a central vein is not possible, peripheral venous access can be used.
Severe arrhythmias when oral treatment is not appropriate, with the exception of cardiopulmonary resuscitation in the case of cardiac arrest associated with ventricular fibrillation refractory to electrical shock therapy:
Infusion via central venous access
Loading dose: an average of 5 mg/kg in glucose solution, preferably using an electric syringe, administered over 20 minutes to 2 hours; Repeat administration 2 or 3 times over a 24-hour period. The short duration of action of the drug requires continuous infusion.
Maintenance dose: 10-20 mg/kg/day (average 600-800 mg/24 hours, can be increased to 1.2 g/24 hours) in 250 ml glucose solution, for several days.
The transition to oral treatment (3 tablets of 200 mg per day) begins on the first day of infusion. This dose can be increased to 4 or even 5 tablets per day.
Cardiopulmonary resuscitation in cases of cardiac arrest associated with ventricular fibrillation resistant to electropulse therapy
When taking the drug in this situation, the use of a central venous catheter is recommended if immediately available; otherwise, the drug can be administered through a peripheral venous approach, using the largest peripheral vein with the strongest blood flow.
The initial intravenous dose is 300 mg (or 5 mg/kg), diluted in 20 ml of 5% glucose solution, administered quickly.
An additional dose of 150 mg (or 2.5 mg/kg) administered intravenously may be used if ventricular fibrillation persists.
Do not add any other medications to the syringe.
Side effects
Very often (³ 10%), often (³ 1% -< 10%), нечасто (³ 0,1% - < 1%), редко (³ 0,01% - < 0,1%), очень редко (< 0,01%)
Often
Nausea
Flushes of blood
Thyroid disease: In the absence of any clinical signs of thyroid dysfunction, “dissociated” thyroid hormone levels (elevated T4, normal or slightly decreased T3) should not be a reason to discontinue treatment with this drug
Bradycardia
Inflammatory reactions such as superficial phlebitis when administered directly through a peripheral vein, injection site reactions (pain, erythema, swelling, necrosis, extravasation, infiltration, inflammation, phlebitis and cellulitis)
Usually moderate and transient decrease in blood pressure, cases of severe hypotension or collapse, in particular after overdose or after too rapid administration of the drug
Hypothyroidism (decreased activity of the thyroid gland), usually accompanied by symptoms such as weight gain, sensitivity to cold, apathy, drowsiness, a clear increase in the level of thyroid-stimulating hormone (thyroid function returns to normal within 1-3 months after stopping treatment); discontinuation of the drug is not necessary if treatment with Cordarone is necessary, in which case it is possible to continue using the drug in combination with thyroid hormone replacement therapy using L-thyroxine, using the level of thyroid-stimulating hormone to determine the dosage
Hyperthyroidism (increased activity of the thyroid gland), usually accompanied by mild symptoms: unexplained weight loss, decreased antianginal and/or antiarrhythmic effectiveness, mental symptoms in elderly patients, thyrotoxicosis. A decrease in thyroid-stimulating hormone levels will confirm the diagnosis. The use of Cordarone should be discontinued until the clinical picture has recovered within 3-4 weeks. In severe cases, death is possible, and appropriate treatment must be prescribed immediately. For thyrotoxicosis, corticosteroid therapy (1 mg/kg) for about 3 months may be recommended. Cases of hyperthyroidism have been reported up to several months after discontinuation of amiodarone.
Very rarely
Severe bradycardia and, even less frequently, sinus node arrest, especially in elderly patients
Proarrhythmic effect
Acute liver damage with high levels of serum transaminases and/or jaundice (sometimes fatal); treatment with Cordarone should be discontinued
Moderate, isolated increase in transaminase levels (1.5-3.0 times the normal range), returns to normal after dosage reduction or spontaneously
Chronic liver damage during long-term treatment (oral). Histological data correspond to those for pseudoalcoholic hepatitis. Since laboratory and clinical signs are variable (intermittent hepatomegaly, increased serum transaminase levels 1.5 to 5 times higher than normal), regular monitoring of liver function is warranted. The diagnosis of chronic liver damage should be considered if there is an increase, even moderate, in the level of transaminases in the blood during a treatment period exceeding 6 months. Clinical and laboratory deviations from the norm x, as a rule, return to normal after treatment is discontinued. Several cases of irreversible changes have been reported.
Anaphylactic shock
Benign intracranial hypertension (pseudotumor cerebri)
Acute respiratory distress syndrome, usually associated with interstitial pneumopathy, in some cases fatal, sometimes immediately after surgery (possible interaction with high doses of oxygen); the issue of discontinuation of Cordarone and the advisability of treatment with corticosteroids should be considered
Bronchospasm and/or apnea in cases of severe respiratory failure, in particular in patients with asthma
Increased sweating, hair loss
Syndrome of inappropriate antidiuretic hormone secretion
Tides
Not known
Quincke's edema, urticaria, fever
Lower back pain, back pain
Ventricular tachycardia of the “feast” type (torsades de pointes)
Cases of angioedema and/or allergic rash
Eczema, severe, sometimes fatal, skin reactions: epidermal necrolysis (Lyell's syndrome), Stevens-Johnson syndrome
Bullous dermatitis
DRESS syndrome (drug reaction skin reaction accompanied by eosinophilia and systemic manifestations)
Pancreatitis, acute pancreatitis
Neutropenia, agranulocytosis
State of confusion, delusion, hallucination
Loss of libido
Severe respiratory failure, acute respiratory failure, sometimes fatal
Contraindications
Sinus bradycardia or sinoatrial block in patients without a pacemaker
Sick sinus syndrome in patients without a pacemaker (risk of sinus arrest)
High degree of atrioventricular conduction impairment in patients without an artificial pacemaker
Hyperthyroidism due to possible exacerbation provoked by Cordarone
Known hypersensitivity to iodine, amiodarone or any of the excipients
Circulatory collapse
Heart failure, cardiomyopathy
Severe respiratory failure
Severe hypotension
Premature and full-term newborns, children under 3 years of age due to the presence of benzyl alcohol
Pregnancy and lactation
Class Ia antiarrhythmic drugs (quinidine, hydroquinidine,
disopyramide)
Class III antiarrhythmics (sotalol, dofetilide, ibutilide)
Other drugs such as arsenic compounds, bepridil, cisapride, citalopram, escitalopram, difemanil, dolasetron IV, domperidone, dronedarone, erythromycin IV, levofloxacin, mequitazine, mizolastine, moxifloxacin, prusalopride, spiramycin IV, toremifene, IV vincamine (see “Drug Interactions”)
Telaprevir
Cobicistat
These contraindications do not apply to the use of Cordarone in patients for resuscitation of cardiac arrest associated with ventricular fibrillation in cases where the use of a defibrillator has not stopped ventricular fibrillation.
Drug interactions
Antiarrhythmic drugs
Many antiarrhythmic drugs have a suppressive effect on the automaticity, conductivity and contractility of the myocardium. The combined use of different classes of antiarrhythmic drugs may be beneficial, but this therapeutic approach is often problematic and requires ECG and close clinical monitoring. The combined use of antiarrhythmic drugs that cause bidirectional tachycardia (pirouette tachycardia) (amiodarone, disopyramide, quinidines, sotalol, etc.) is contraindicated.
Concomitant use of antiarrhythmic agents of the same class is not recommended except in exceptional circumstances due to the higher risk of adverse cardiac side effects.
The use of amiodarone in combination with drugs with negative inotropic properties that cause bradycardia and/or slow atrioventricular conduction is problematic and requires clinical and ECG monitoring.
Medicines that can cause torsade de pointes (TdP)
This serious arrhythmia can be caused by many medications, whether they are antiarrhythmic drugs or not. Hypokalemia is a predisposing factor, as is bradycardia, as well as congenital or acquired pre-existing long QT syndrome.
Such drugs include class Ia and class III antiarrhythmics and some antipsychotics. For dolasetron, erythomycin, spiramycin and vincamine, this interaction occurs only with intravenous forms of the drug. In general, the use of two torsadogenic drugs that can cause torsade de pointes at the same time is contraindicated.
However, this does not apply to some of these agents, which are considered absolutely necessary and, rather than contraindicated, their use in combination with other torsadogenic drugs that can cause torsade de pointes is not recommended. These include:
Methadone
Neuroleptics.
Many drugs can cause bradycardia, including class Ia antiarrhythmics, beta blockers, some class III antiarrhythmics, some calcium antagonists, digitalis, pilocarpine, and anticholinesterase drugs.
Effect of amiodarone on other drugs
Amiodarone and/or its metabolite, desetyl-amiodarone, inhibit CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein and may increase the effects of their substrates.
Given the long-acting effects of amiodarone, these interactions may be observed for several months after discontinuation of treatment.
Effect of other drugs on amiodarone
CYP3A4 inhibitors and CYP2C8 inhibitors may potentially inhibit the metabolism of amiodarone and thus increase exposure.
CYP3A4 inhibitors (eg, grapefruit juice and certain drugs) should preferably not be used during treatment with amiodarone.
Contraindicated combinations
Class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide)
Class III antiarrhythmics (dofetilide, ibutilide, sotalol)
Other drugs such as arsenic compounds, bepridil, cisapride, citalopram, escitalopram, difemanil, dolasetron IV, domperidone, dronedarone, erythromycin IV, levofloxacin, mequitazine, mizolastine, moxifloxacin, prucalopride, spiramycin IV, toremifene, Vincamine IV.
The risk of ventricular arrhythmias, in particular tachycardia of the “pirouette” type, increases.
Telaprevir
Impaired conduction and automaticity of the heart with a risk of increased bradycardia.
Cobicistat
Increased risk of side effects caused by amiodarone due to decreased metabolism.
Sofosbuvir
Only patients receiving dual therapy with daclatasvir/sofosbuvir or ledipazvir/sofosbuvir may develop bradycardia, symptomatic or even fatal.
If the use of these combinations cannot be avoided, clinical monitoring and ECG are necessary, especially during the first few weeks of dual therapy.
CYP3A4 substrates
Amiodarone is a CYP3A4 inhibitor and increases plasma concentrations of CYP3A4 substrates, potentially increasing the toxicity of these substrates.
Cyclosporine
An increase in the concentration of cyclosporine in the blood, due to a decrease in metabolism in the liver, with the risk of developing nephrotoxic effects.
The concentration of cyclosporine in the blood should be analyzed, renal function monitored and the dosage of cyclosporine adjusted during treatment with Cordarone.
Injectable diltiazem
Fingolimod
Potentiation of bradycardia-inducing effects with possible lethal results. This is especially true for beta blockers, which inhibit adrenergic compensation mechanisms.
Monitoring of clinical parameters and continuous ECG monitoring is necessary for 24 hours after taking the first dose.
Injectable verapamil
Risk of bradycardia and atrioventricular heart block. If the use of this combination cannot be avoided, strict clinical observation and continuous ECG monitoring are necessary.
Increased risk of ventricular arrhythmias, in particular torsade de pointes. If possible, one of the two types of treatment should be discontinued. If the use of this combination cannot be avoided, pre-measurement of the QT interval and ECG monitoring during treatment are necessary.
Neuroleptics that can provoke tachycardia of the “pirouette” type:
amisulpride, chlorpromazine, cyamemazine, droperidol, flupenthixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperone, pipothiazine, sertindole, sulpride, sultopride, tiapride, zuclopenthixol. Increased risk of ventricular arrhythmias, in particular torsade de pointes.
Increased risk of ventricular arrhythmias, in particular torsade de pointes.
Fluoroquinolones other than levofloxacin and moxifloxacin (combinations contraindicated):
Increased risk of ventricular arrhythmia, especially torsade de pointes. Stimulant laxatives
Increased risk of developing ventricular arrhythmia, especially the “pirouette” type (hypokalemia is a predisposing factor).
Before taking the drug, it is necessary to correct any hypokalemia, take an ECG, and conduct clinical monitoring along with electrolyte monitoring.
Fidaxomicin
Increased concentration of fidoxomicin in blood plasma.
Combinations requiring precautions during use
P-glycoprotein substrates
Amiodarone is a P-glycoprotein (P-gp) inhibitor. Combination administration with P-gp substrates may result in increased exposure to these substrates.
Digitalis preparations
Suppression of automaticity (significant bradycardia) and disturbance of atrioventricular conduction.
When using digoxin, its blood level may increase due to the slow elimination of digoxin from the body; an ECG and clinical observation are required.
If necessary, you can monitor the level of digoxin in the blood and adjust the dosage of digoxin.
Dabigatran
Increased plasma concentrations of dabigatran, high risk of bleeding.
If dabigatran is used in the postoperative period, clinical monitoring should be carried out and, if necessary, the dosage of dabigatran should be adjusted; the dosage should not exceed 150 mg/day.
CYP2C9 substrates
Amiodarone increases plasma concentrations of CYP2C9 substrates such as vitamin K antagonists and phenytoin.
Vitamin K antagonists
Increased vitamin K antagonist effect and high risk of bleeding.
The International Normalization Ratio (INR) should be checked more frequently. The dosage of the vitamin K agonist should be adjusted during the period of treatment with amiodarone and for 8 days after discontinuation of treatment.
Phenytoin (and by extrapolation, fosphenytoin)
An increase in the concentration of phenytoin in plasma with the manifestation of symptoms of overdose, in particular neurological symptoms (decreased metabolism of phenytoin in the liver).
Clinical observation and monitoring of phenytoin plasma concentrations should be carried out and, if necessary, the phenytoin dosage should be adjusted.
CYP2D6 substrates
Flecainide
Amiodarone increases plasma concentrations of flecainide through inhibition of cytochrome CYP2D6. The dosage of flecainide should be adjusted.
CYP3A4 substrates
Amiodarone is an inhibitor of CYP3A4 and increases plasma concentrations of substrates of this cytochrome, potentially increasing the toxicity of these substrates.
Statins (simvastatin, atorvastatin, lovastatin)
The risk of muscle toxicity (eg, rhabdomyolysis) is increased with coadministration of amiodarone as statins are broken down by CYP3A4. The use of another statin that is not affected by this interaction is recommended.
Other drugs metabolized by CYP3A4 (lidocaine, tacrolimus, sildenafil, midazolam, dihydroergotamine, ergotamine, colchicine, triazolam)
Amiodarone is an inhibitor of CYP3A4 and increases plasma concentrations of these molecules, potentially increasing the risk of toxicity of these substances.
Lidocaine
Risk of increased lidocaine plasma concentrations, which may lead to neurological and cardiac side effects due to reduced hepatic metabolism by amiodarone.
Clinical observation and ECG should be performed and, if necessary, monitoring of lidocaine plasma concentrations. If necessary, the dosage of lidocaine should be adjusted during the treatment period and after discontinuation of amiodarone.
Tacrolimus
An increase in the concentration of tacrolimus in the blood due to inhibition of its metabolism by amiodarone.
During the period of combination treatment with amiodarone and after completion of treatment with this drug, the level of tacrolimus concentration in the blood should be analyzed, renal function monitored, and the dosage of tacrolimus adjusted.
Beta blockers (except esmolol and sotalol)
Impaired automatism and conduction of the heart (compensatory sympathetic mechanisms are suppressed). Clinical and ECG monitoring.
Beta blockers (except esmolol and sotalol)
Disorders of automaticity and cardiac conduction (suppression of sympathetic compensatory mechanisms). Clinical and ECG monitoring is required.
Beta blockers for heart failure (bisoprolol, carvedilol, metoprolol, nebivolol)
Impaired automaticity and cardiac conduction with a risk of significant bradycardia. Increased risk of developing ventricular arrhythmia, in particular tachycardia of the “pirouette” type. Clinical and regular ECG monitoring.
Impaired contractility, automatism and conduction (suppression of compensatory sympathetic mechanisms). ECG and clinical monitoring are necessary.
Diltiazem for oral administration
Risk of bradycardia or atrioventricular heart block, especially in elderly patients. ECG and clinical monitoring required.
Oral verapamil
Risk of bradycardia or atrioventricular heart block, particularly in elderly patients. ECG and clinical monitoring required.
Some macrolides (azithromycin, clarithromycin, roxithromycin)
Increased risk of ventricular arrhythmia, in particular torsade de pointes. Clinical observation and ECG should be performed during combination treatment with amiodarone.
Hypokalemic agents: hypokalemic diuretics (alone or in combination), amphotericin B (iv), glucocorticosteroids (systemic route), tetracosactide
Increased risk of developing ventricular arrhythmia, in particular tachycardia of the “pirouette” type (hypokalemia is a predisposing factor).
Bring the level of potassium in the blood to normal before prescribing the drug, conduct an ECG and clinical observation, and also monitor the content of electrolytes.
Drugs that cause bradycardia
Increased risk of ventricular arrhythmia, in particular torsade de pointes. Clinical observation and ECG should be performed.
Orlistat
Risk of decreased plasma concentrations of amiodarone and its active metabolite.
Clinical observation and, if necessary, ECG should be performed.
Tamsulosin
Risk of adverse effects caused by tamsulosin due to inhibition (slowing) of hepatic metabolism.
Clinical monitoring should be carried out and tamsulosin dosage adjusted during the treatment period with the enzyme inhibitor and after discontinuation of use, if necessary.
Voriconazole
Increased risk of ventricular arrhythmia, in particular torsade de pointes, as amiodarone metabolism may be reduced.
Clinical monitoring and ECG should be performed and amiodarone dosage adjusted if necessary.
Please pay attention to the following combinations
Pilocarpine
Risk of significant bradycardia (common adverse effects caused by bradycardia).
special instructions
Cautions regarding route of administration
Infusion through central venous access: for severe types of arrhythmia when oral treatment is not applicable, with the exception of cases of cardiopulmonary resuscitation for ventricular fibrillation resistant to electrical impulse therapy in patients with cardiac arrest.
Cordarone® injection must be administered through the central venous route because administration through a peripheral vein may cause local reactions such as superficial phlebitis. Cordarone®, solution for injection should be administered exclusively as an infusion. Even very slow injection directly into a vein can worsen hypotension, heart failure and severe respiratory failure (see Side Effects).
Cardiopulmonary resuscitation for ventricular fibrillation resistant to electrical impulse therapy in patients with cardiac arrest
Administration via a peripheral vein is generally not recommended due to hemodynamic risk (severe hypotension, vascular collapse); the infusion should be administered through a central vein whenever possible
The use of a central venous catheter is recommended if immediately available; otherwise, the drug can be administered through a peripheral vein, using the largest peripheral vein with the largest possible blood flow
Monitoring in the intensive care unit with continuous monitoring of blood pressure and ECG should be established as soon as possible
Do not add any other medications to the syringe.
If treatment with Cordarone is to be continued, then it should be administered as a central venous infusion with continuous monitoring of blood pressure and ECG.
Cardiac disorders
Cases of development of new arrhythmia and worsening of pre-existing arrhythmia have been reported (see "Side effects")
A proarrhythmogenic effect of amiodarone may occur, especially in the presence of factors known to prolong the QT interval, such as interactions with other drugs (see Drug Interactions) and/or hypokalemia. The risk of torsade de pointes (TdP) is lower with amiodarone compared with other antiarrhythmic agents in patients with the same level of QT prolongation.
Serious skin disorders
Life-threatening or even fatal skin reactions such as Steven-Johnson syndrome or toxic epidermal necrolysis may occur. If signs or symptoms suggestive of such conditions occur (eg, developing skin rash with blisters or mucosal lesions), amiodarone should be discontinued immediately.
Severe bradycardia
Severe, possibly life-threatening bradycardia and serious cardiac conduction abnormalities have been reported in patients taking amiodarone in combination with sofosbuvir or other direct-acting antivirals (DAAs) intended to treat hepatitis C, such as daclatasvir, simeprevir, or ledipazvir. The combined use of these drugs with amiodarone is not recommended.
If concomitant use of these drugs with amiodarone cannot be avoided, patients should be closely monitored from the start of its use with sofosbuvir or in combination with other DAAs. After starting sofosbuvir, patients at high risk of bradyarrhythmia should be under appropriate, continuous monitoring for at least 48 hours after starting sofosbuvir. Due to the long-lasting effects of amiodarone, patients who have discontinued amiodarone within the last few months should be closely monitored before initiating treatment with sofosbuvir alone or in combination with other DAAs.
Patients taking these drugs to treat hepatitis C in combination with amiodarone, and with or without other drugs that lower heart rate, should be warned about symptoms of bradycardia and severe cardiac conduction disturbances. It is also necessary to warn patients to immediately consult a doctor if such symptoms are detected.
Lung disorders
There are several known cases of the development of interstitial pneumonitis after intravenous administration of the drug Cordarone. The development of shortness of breath or a dry cough, either accompanied or not accompanied by a deterioration in general condition, indicates the possibility of pulmonary toxicity, such as interstitial pneumopathy, and requires radiological examination (see "Side effects").
In addition, several cases of acute respiratory distress syndrome have been observed immediately after surgery in patients treated with amiodarone. In this regard, strict monitoring of such patients is recommended during artificial ventilation.
Liver disorders
Severe hepatocellular injury, sometimes fatal, may occur within 24 hours of starting treatment with injectable amiodarone (see Side Effects). Regular monitoring of liver function is recommended at the beginning of treatment and then regularly throughout treatment with Cordarone (see “Side effects”).
Excipients
This medicinal product contains 60 mg of benzyl alcohol in a 3 ml ampoule. Benzyl alcohol may cause toxic or anaphylactoid reactions in infants and children under 3 years of age.
When taking medications containing benzyl alcohol, premature and full-term newborns may develop fatal asphyxia syndrome in newborns with fatal cases (with signs of sudden onset of shortness of breath, hypotension, bradycardia and cardiovascular collapse).
Special precautions for use
Electrolyte disturbances, especially hypokalemia: It is important to consider conditions associated with the risk of hypokalemia, hypokalemia may contribute to the proarrhythmic effect. Hypokalemia should be corrected before starting amiodarone.
Apart from emergency situations, injectable amiodarone should be administered only in specialized hospital settings and with continuous monitoring (ECG, blood pressure).
Anesthesia
Before surgery, the anesthesiologist should be informed that the patient is being treated with Cordarone.
Long-term treatment with amiodarone increases the risk of hemodynamic compromise associated with general or local anesthesia. Adverse reactions include, but are not limited to, bradycardia, hypotension, decreased cardiac output, and cardiac conduction disturbances.
The combination of Cordarone (see "Drug Interactions") with beta-blockers, except sotalol (a contraindicated combination) and esmolol (a combination requiring precautions during use), verapamil and diltiazem, is possible only for the prevention of life-threatening ventricular arrhythmias, and during cardiopulmonary resuscitation in the event of cardiac arrest associated with ventricular fibrillation resistant to electropulse therapy.
Pregnancy
No teratogenic effects have been identified in animal studies and therefore no malformations are expected to occur in humans. To date, animal studies have shown that substances that cause malformations in humans are teratogenic in animals.
At the moment, there are insufficient clinical data to assess the possible teratogenic effects of amiodarone when administered to humans in the first trimester of pregnancy.
Since the fetal thyroid gland begins to bind iodine at 14 weeks after the onset of amenorrhea, amiodarone is not expected to have an effect on the fetal thyroid gland if administered before this period.
Excess iodine with amiodarone use after this period can lead to hypothyroidism, which may be evident in laboratory tests or even in the clinical manifestation of goiter.
Thus, the use of this drug is contraindicated from the second trimester of pregnancy.
Precautions should be taken when using injection solutions containing benzyl alcohol during pregnancy, since benzyl alcohol crosses the placental barrier.
Lactation
Amiodarone and its metabolite in combination with iodine are excreted into breast milk in higher concentrations than in maternal plasma. Due to the risk of hypothyroidism in the infant, breastfeeding is contraindicated when using this drug.
Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms
Not applicable.
Overdose
Symptoms: There is no information on overdose of intravenous Cordarone. There is very little information available regarding acute overdose with oral Cordarone. Several cases of sinus bradycardia, ventricular arrhythmias, in particular torsade de pointes, and liver damage have been reported.
Treatment: symptomatic. Considering the pharmacokinetic profile of the drug, it is recommended to monitor the patient’s condition for a sufficiently long time, especially his cardiac activity. Amiodarone and its metabolites are not amenable to dialysis.
Shelf life
Do not use after the expiration date stated on the packaging.
Conditions for dispensing from pharmacies
On prescription
The injection solution is intended for use only in a hospital.
Detailed instructions for use are published on this page. Cordarona. The available dosage forms of the drug are listed (200 mg tablets, injections in ampoules for intravenous injection), as well as its analogues. Information is provided on the side effects that Cordarone can cause and on interactions with other medications. In addition to information about the diseases for the treatment and prevention of which the drug is prescribed (arrhythmia, tachycardia, atrial and ventricular fibrillation), administration algorithms, possible dosages for adults and children are described in detail, the possibility of use during pregnancy and breastfeeding is clarified. The abstract for Cordarone is supplemented by reviews from patients and doctors. Composition of the drug.
Instructions for use and dosage
Pills
When prescribing the drug in a loading dose, various schemes can be used.
When used in a hospital, the initial dose, divided into several doses, ranges from 600-800 mg per day to a maximum of 1200 mg per day until a total dose of 10 g is reached (usually over 5-8 days).
For outpatient use, the initial dose, divided into several doses, ranges from 600 mg to 800 mg per day until a total dose of 10 g is reached (usually within 10-14 days).
The maintenance dose may vary between patients from 100 mg per day to 400 mg per day. The minimum effective dose should be used according to the individual therapeutic effect.
Because Amiodarone has a very long half-life, the drug can be taken every other day or take breaks from taking it 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.
Ampoules
Cordarone for intravenous administration is intended for use in cases where rapid achievement of an antiarrhythmic effect is required, or if it is impossible to administer the drug orally.
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 or simultaneously administered other drugs through the same venous access. The drug should be administered only in diluted form. To dilute 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 that are less than those obtained by diluting 2 ampoules in 500 ml of 5% dextrose (glucose).
To avoid injection site reactions, Cordarone should be administered through a central venous catheter, except in cases of cardiac resuscitation for ventricular fibrillation resistant to cardioversion, when, in the absence of central venous access, the drug can be administered into the peripheral veins (the largest peripheral vein with maximum blood flow).
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)
The drug is administered intravenously (dropper) through a central venous catheter.
The loading dose is usually 5 mg/kg body weight in 250 ml of a 5% dextrose (glucose) solution, administered over 20-120 minutes, if possible using an electronic pump. This dose can be repeated 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 the injection form of Cordarone, it is recommended to switch to constant IV drip administration of the drug.
Maintenance doses: 10-20 mg/kg/24 hours (usually 600-800 mg, but can be increased to 1200 mg over 24 hours) in 250 ml of 5% dextrose (glucose) solution for several days. From the first day of infusion, a gradual transition to taking Cordarone orally at a dose of 600 mg (3 tablets) per day should begin. The dose can be increased to 800-1000 mg (4-5 tablets) per day.
Cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to cardioversion
The drug is administered intravenously. The first dose is 300 mg (or 5 mg/kg) in 20 ml of a 5% dextrose (glucose) solution. If fibrillation does not stop, then additional administration of Cordarone intravenously in a bolus at a dose of 150 mg (or 2.5 mg/kg) is possible.
Compound
Amiodarone hydrochloride + excipients.
Release forms
Tablets 200 mg.
Solution for intravenous administration (injections in injection ampoules).
Cordaron- antiarrhythmic drug. Amiodarone (the active ingredient of the drug Cordarone) belongs to class 3 (class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action, because in addition to the properties of class 3 antiarrhythmics (potassium channel blockade), it has the effects of class 1 antiarrhythmics (sodium channel blockade), class 4 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.
The antiarrhythmic effect of the drug is due to 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 3 antiarrhythmics according to the Vaughan-Williams classification); a decrease in the automaticity of the sinus node, leading to a decrease in heart rate; non-competitive blockade of alpha and beta adrenergic receptors; slowing of sinoatrial, atrial and AV conduction, more pronounced with tachycardia; no changes in ventricular conductivity; an increase in refractory periods and a decrease in the excitability of the myocardium of the atria and ventricles, as well as an increase in the refractory period of the AV node; slowing down conduction and increasing the duration of the refractory period in additional AV conduction bundles.
In addition, Cordarone has the following properties: no 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
Bioavailability after oral administration in different patients ranges from 30% to 80% (average value about 50%). 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. An equilibrium state is achieved after 1 to several months, depending on the individual characteristics of the patient. The pharmacokinetics of the drug explain the use of loading doses, which are aimed at quickly achieving the required level of tissue penetration at which the therapeutic effect of amiodarone is manifested. Metabolized in the liver. The main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. Amiodarone elimination begins within a few days. It is excreted mainly through the intestines.
Indications
Pills
Relapse prevention:
- life-threatening ventricular arrhythmias and ventricular fibrillation (treatment should begin in the hospital with careful cardiac monitoring);
- supraventricular paroxysmal tachycardias, incl. documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with organic heart diseases; documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients without organic heart disease, when antiarrhythmic drugs of other classes are not effective or there are contraindications to their use; documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with WPW syndrome;
- atrial fibrillation (atrial fibrillation) and atrial flutter.
Prevention of sudden arrhythmic death in high-risk patients:
- patients after a recent myocardial infarction with more than 10 ventricular extrasystoles per hour, clinical manifestations of chronic heart failure and reduced left ventricular ejection fraction (<40%).
Solution
- relief of attacks of ventricular paroxysmal tachycardia;
- relief of attacks of supraventricular paroxysmal tachycardia with a high frequency of ventricular contractions (especially against the background of WPW syndrome);
- relief of paroxysmal and stable forms of atrial fibrillation (atrial fibrillation) and atrial flutter;
- Cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to cardioversion.
Contraindications
- SSS (sinus bradycardia, sinoatrial block) except in cases of correction with an artificial pacemaker (danger of “stopping” the sinus node);
- 2nd and 3rd degree AV block in the absence of a permanent artificial pacemaker (pacemaker);
- two- and three-bundle blockades in the absence of a pacemaker;
- hypokalemia, hypomagnesemia;
- interstitial lung diseases;
- 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 polymorphic ventricular tachycardia of the "pirouette" type: class 1 A antiarrhythmics (quinidine, hydroquinidine, disopyramide, procainamide); class 3 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; antimalarials (quinine, chloroquine, mefloquine, halofantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones;
- children and adolescents under 18 years of age (efficacy and safety have not been established);
- pregnancy;
- lactation period;
- hypersensitivity to iodine and/or amiodarone.
special instructions
Side effects of Cordarone are dose-dependent, therefore, to minimize the possibility of their occurrence, the drug should be used in the minimum effective dose.
During treatment, patients should avoid exposure to direct sunlight or take protective measures (eg, using sunscreen, wearing appropriate clothing).
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), the level of liver transaminases and other indicators of liver function.
In addition, due to the fact that Cordarone can cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, before taking amiodarone, a clinical and laboratory (TSH level) examination should be performed to identify dysfunctions and diseases of the thyroid gland. During treatment with amiodarone and for several months after its cessation, regular examinations are required to identify 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, an increase in the frequency of ventricular fibrillation and/or an increase in the threshold for the response of a pacemaker or implanted defibrillator has been reported, which may reduce their effectiveness. Therefore, before starting or during treatment with Cordarone, 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, indicates 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 changes in the ECG: prolongation of the QT interval, QTc (corrected), possible appearance of U waves. An increase in the QTc interval 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 2nd and 3rd degree AV block, sinoatrial block or double-bundle intraventricular block develops, treatment should be discontinued. If 1st degree AV block occurs, increased clinical monitoring is required.
Although the occurrence of arrhythmias or worsening of existing rhythm disturbances has been noted, the proarrhythmogenic effect of amiodarone is weak, less than that of most antiarrhythmic drugs, 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 T3, T4 and TSH in the blood plasma.
Before surgery, the anesthesiologist should be informed that the patient is receiving Cordarone. Prolonged treatment with Cordarone may increase the hemodynamic risk inherent in local or general anesthesia. This especially applies to its bradycardic and hypotensive effects, decreased cardiac output and conduction disorders.
In addition, in rare cases, acute respiratory distress syndrome was observed in patients receiving Cordarone immediately after surgery. During mechanical ventilation, such patients require careful monitoring.
Impact on the ability to drive vehicles and operate machinery
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.
Side effect
- moderate dose-dependent bradycardia
- 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; these effects are observed mainly in cases of Cordarone use in conjunction with drugs that prolong the QTc interval or with electrolyte imbalances; in the light of available data, it is impossible 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 (mainly in patients with sinus node dysfunction and elderly patients)
- progression of heart failure (with long-term use)
- nausea, vomiting
- loss of appetite
- dullness or loss of taste
- a feeling of heaviness in the epigastrium (occurs mainly at the beginning of treatment, disappears after reducing the dose)
- interstitial or alveolar pneumonitis
- bronchiolitis obliterans with pneumonia (sometimes fatal)
- pleurisy
- bronchospasm (in patients with severe respiratory failure, especially in patients with bronchial asthma)
- acute respiratory distress syndrome (sometimes fatal and sometimes immediately after surgery; possible interaction with high doses of oxygen)
- pulmonary hemorrhage
- microdeposits in the corneal epithelium consisting of complex lipids, including lipofuscin
- Optic neuritis
- hypothyroidism (weight gain, chilliness, apathy, decreased activity, drowsiness, bradycardia that is excessive compared to the expected effect of amiodarone)
- hyperthyroidism, which may appear during and after treatment (cases of hyperthyroidism that developed several months after discontinuation of amiodarone have been described)
- photosensitivity
- grayish or bluish pigmentation of the skin (this pigmentation slowly disappears after stopping treatment)
- erythema (during radiation therapy)
- skin rash (usually unspecific)
- alopecia
- exfoliative dermatitis (no connection with the drug has been established)
- tremor or other extrapyramidal symptoms
- sleep disorders
- nightmares
- myopathy
- headache
- thrombocytopenia, hemolytic anemia, aplastic anemia
- vasculitis
- several cases of impotence (no connection with the drug has been established).
Drug interactions
Contraindicated combinations
The use of Cordarone as part of combination therapy with drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type is contraindicated, because when combined with amiodarone, the risk of developing this complication and death increases:
- antiarrhythmics: class 1A (quinidine, hydroquinidine, disopyramide, procainamide), class 3 (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; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with intravenous administration, spiramycin); azoles; antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole; terfenadine; fluoroquinolones (in particular moxifloxacin).
- with beta-blockers, with blockers of slow calcium channels that slow down heart rate (verapamil, diltiazem), because there is a risk of developing disorders of automatism (severe bradycardia) and conduction;
- with laxatives that stimulate intestinal motility, which can cause hypokalemia, which increases the risk of developing torsades de pointes. During treatment with Cordarone, laxatives from other groups should be used.
Combinations that require caution when using
With drugs that can cause hypokalemia:
- diuretics that cause hypokalemia (in monotherapy or combination);
- amphotericin B (iv);
- glucocorticosteroids (GCS) for systemic use;
- tetracosactide.
The risk of developing ventricular arrhythmias increases, especially ventricular tachycardia of the “pirouette” type (hypokalemia is a predisposing factor). It is necessary to monitor the content of electrolytes in the blood, and, if necessary, correct hypokalemia, constant clinical observation and ECG monitoring. In the event of the development of ventricular tachycardia of the "pirouette" type, antiarrhythmic drugs should not be used (ventricular pacing should be started, possibly intravenous administration of magnesium salts).
With procainamide
Amiodarone may increase plasma concentrations of procainamide and its metabolite N-acetyl procainamide, which may increase the risk of procainamide side effects.
With indirect anticoagulants
Amiodarone increases warfarin concentrations by inhibiting the CYP2C9 isoenzyme. When warfarin is combined with amiodarone, the effects of the indirect anticoagulant may be enhanced, which increases the risk of bleeding. The prothrombin time (INR) should be monitored more frequently and the anticoagulant dose adjusted both during treatment with amiodarone and after its discontinuation.
With cardiac glycosides (digitalis preparations)
Impairments of automatism (severe bradycardia) and atrioventricular conduction may occur. 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 ECG manifestations of digitalis intoxication. Digoxin dosages may need to be reduced.
With esmolol
Possible disturbances in contractility, automaticity and conductivity (suppression of compensatory reactions of the sympathetic nervous system). Clinical and ECG monitoring is required.
With phenytoin (and, by extrapolation, with fosphenytoin)
Amiodarone can increase plasma concentrations of phenytoin due to inhibition of the CYP2C9 isoenzyme, therefore, when combining phenytoin with amiodarone, an overdose of phenytoin may develop, which can lead to the appearance of neurological symptoms; clinical monitoring is necessary and, at the first signs of overdose, a reduction in the dose of phenytoin; it is advisable to determine the concentration of phenytoin in the blood plasma.
With drugs metabolized by the CYP3A4 isoenzyme
When amiodarone, which is 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 dose reduction of these drugs:
- cyclosporine: there may be an increase in the concentration of cyclosporine in the blood plasma, associated with a decrease in the metabolism of the drug in the liver, which may increase the nephrotoxic effect of cyclosporine. It is necessary to determine the concentration of cyclosporine in the blood, monitor kidney function and correct the dosage regimen of cyclosporine during treatment with amiodarone and after discontinuation of the drug.
- fentanyl: when combined with amiodarone, the pharmacodynamic effects of fentanyl may be enhanced and the risk of developing its toxic effects may increase.
- 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, statins, including simvastatin (increased risk of muscle toxicity, rhabdomyolysis, and therefore the dose of simvastatin should not exceed 20 mg per day; if it is ineffective, you should switch to another statin that is not metabolized by CYP3A4).
With orlistat
There is a risk of a decrease in the concentration of amiodarone and its active metabolite in the blood plasma. Clinical and, if necessary, ECG monitoring is necessary.
With clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine
There is a risk of developing excessive bradycardia (cumulative effects).
With cimetidine, grapefruit juice
There is a slowdown in the metabolism of amiodarone and an increase in its plasma concentrations, and an increase in the pharmacodynamic and side effects of amiodarone is possible.
With drugs for inhalation anesthesia
The possibility of developing the following severe complications in patients receiving amiodarone during anesthesia has been reported: bradycardia (resistant to atropine administration), arterial hypotension, conduction disturbances, decreased cardiac output. Very rare cases of severe respiratory complications (adult acute respiratory distress syndrome), sometimes fatal, have been observed that developed immediately after surgery, the occurrence of which is associated with high oxygen concentrations.
With radioactive iodine
Amiodarone contains iodine and therefore can interfere with the absorption of radioactive iodine, which can distort the results of radioisotope studies of the thyroid gland.
With rifampicin
Rifampicin is a strong inducer of CYP3A4, therefore, when used together with amiodarone, a decrease in plasma concentrations of amiodarone and desethylamiodarone is possible.
With St. John's wort preparations
St. John's wort is a powerful CYP3A4 inducer. In this regard, it is theoretically possible to reduce the plasma concentration of amiodarone and reduce its effect (clinical data are not available).
With HIV protease inhibitors (including indinavir)
HIV protease inhibitors are CYP3A4 inhibitors, therefore, when used simultaneously with amiodarone, they can increase the concentration of amiodarone in the blood.
With 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.
With dextromethorphan
Dextromethorphan is a substrate of CYP2D6 and CYP3A4. Amiodarone inhibits CYP2D6 and may theoretically increase plasma concentrations of dextromethorphan.
Analogues of the drug Cordarone
Structural analogues of the active substance:
- Amiodarone;
- Amiocordin;
- Vero Amiodarone;
- Cardiodarone;
- Opacordan;
- Rhythmiodarone;
- Sedakoron.
Analogs by pharmacological group (antiarrhythmic drugs):
- Adenocor;
- Allapinin;
- Asparkam;
- Bretylate;
- Hypertonplant (Gnafalin);
- Dinexan;
- Difenin;
- Cardiodarone;
- Quinidin Durules;
- Lidocaine;
- Moracizine;
- Multaq;
- Neo Gilurithmal;
- Nibentan;
- Novocainamide;
- Pamaton;
- Panangin;
- Procainamide Eskom;
- Propanorm;
- Propafenone;
- Profenan;
- Ritalmex;
- Rhythmiodarone;
- Rhythmodan;
- Rhythmonorm;
- Sedakoron;
- Trimecaine;
- Ethacizin;
- Ethmozin.
Use in elderly patients
Use with caution in elderly patients (high risk of developing severe bradycardia).
Use in children
Contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established).
Use during pregnancy and breastfeeding
Cordarone is contraindicated during pregnancy and lactation (breastfeeding).
Currently available clinical information is insufficient to determine the risk of developmental defects in the embryo when using Cordarone in the 1st 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 thyroid gland of the fetus, Cordarone is contraindicated for use during pregnancy, with the exception of special cases of vital indications (with life-threatening ventricular cardiac arrhythmias).
Recipe for Amiodarone in Latin:
Examples of how to correctly write a prescription for amiodarone in Latin in tablets and ampoules. Amiodarone is an antiarrhythmic drug, most often used to relieve supraventricular tachyarrhythmias.
Amiodarone prescription in Latin for solution in ampoules
Rp.: Sol. Amiodaroni 5% - 3.0 D.t.d.N 4 in amp. S. Administer intravenously, dissolving in 400 ml of 5% glucose solutionPrescription for amiodarone tablets in Latin
Rp.: Tab. Amiodaroni 0.2 D.t.d. N 30 S. 1 tab. * 3 times a day until the total dose is 10 grams, with a further transition to 1 tablet. per dayAmiodarone use regimens: loading and maintenance therapy
Amiodarone loading therapy:
In a hospital setting, 800-1200 mg per day (first dose 600-1200 mg intravenously), then 200 mg * 3 days a day. until the dose reaches 10 grams. In outpatient settings: 600-800 mg in tablets per day until the total dosage is 10 grams (10-14 days).
Maintenance therapy with amiodarone:
This information is intended for specialists and students of medical universities. Do not self-medicate; consult a doctor for qualified help.
General information:
Active substance: Amiodarone (INN)
Pharmacological group: Antiarrhythmic drug
Prescription form: N 107-1/у
Trade names:
- Amiodarone
- Cordaron
- Amiocordin
- Vero-Amiodarone
- Cardiodarone
- Cordaron
- Opacordan
- Rhythmiodarone
- Sedakoron
Important!
In pregnant women, a pronounced teratogenic effect is observed; with prolonged use, it can impair the function of the thyroid gland, such as hyperthyroidism, and can also lead to visual impairment. Contraindicated if you are allergic to iodine.