Cordarone solution. Medicinal reference book geotar
- Instructions for use Cordarone
- Composition of the drug Cordarone
- Indications for the drug Cordarone
- Storage conditions for the drug Cordarone
- Shelf life of the drug Cordarone
ATX Code: Cardiovascular system (C) > Drugs for the treatment of heart diseases (C01) > Antiarrhythmic drugs class I and III (C01B) > Antiarrhythmic drugs class III (C01BD) > Amiodarone (C01BD01)
Release form, composition and packaging
d/v/injection solution. 150 mg/3 ml: amp. 6 pcs.Reg. No.: RK-LS-5-No. 005536 dated 11/10/2011 - Valid
Solution for intravenous injection transparent, pale yellow.
Excipients: benzyl alcohol, polysorbate 80, water, nitrogen.
3 ml - ampoules (6) - contour cell packaging (1) - cardboard boxes.
Description of the drug CORDARONE for injection based on officially approved instructions for use of the drug and made in 2007. Update date: ..0
Class III antiarrhythmic drug. Has antiarrhythmic and antianginal effects.
The antiarrhythmic effect is due to an increase in phase 3 of the action potential of the heart muscle without changing its height or rate of rise (class III according to the Vaughan Williams classification), mainly due to a decrease in potassium current through the channels of the cell membranes of cardiomyocytes and a decrease in the automaticity of the sinus node. Reduces sinus automatism to bradycardia that does not respond to the effects of atropine. The drug non-competitively blocks α- and β-adrenergic receptors. Slows down sinoatrial, atrial and nodal conduction without affecting intraventricular conduction. Cordarone increases the refractory period and reduces myocardial excitability. Slows down the conduction of excitation and lengthens the refractory period of additional atrioventricular pathways. Does not have a negative inotropic effect.
The amount of parenterally administered amiodarone in the blood decreases very quickly as the tissues become saturated with the drug. Cmax is reached 15 minutes after administration of the drug and gradually decreases over 4 hours. Without repeated injections, the drug is gradually eliminated.
When resuming IV administration or when prescribing the drug orally, its tissue reserve is formed.
Amiodarone and its metabolites are not dialyzable.
For intravenous infusion, concentrations below 600 mg/l should not be used. To prepare solutions for intravenous administration, only 5% dextrose (glucose) solution should be used. Cordarone should not be taken into the same syringe with other medications. When infusing the drug, only central venous access (subclavian catheter) should be used. When restoring cardiac activity and breathing during cardiac arrest caused by ventricular fibrillation resistant to external electric shock, it is possible to use peripheral veins in the absence of central venous access.
At severe cardiac arrhythmias, when oral administration of the drug is impossible, with the exception of cases of restoration of cardiac activity and breathing during cardiac arrest caused by ventricular fibrillation resistant to external electric shock:
Loading dose Cordarone is initially 5 mg/kg body weight in an isotonic dextrose solution over 20-120 minutes; if necessary, the drug can be administered 2-3 times a day. The therapeutic effect of Cordarone is relatively short, which requires long-term infusion of the drug.
For maintenance therapy the drug is prescribed as an intravenous infusion for several days at a dose of 600-1200 mg/day in 250 ml of a 5% dextrose solution. From the first day of IV administration of Cordarone, it is advisable to begin a gradual transition to taking the drug orally at a dose of 600-800 mg to 1000 mg/day.
At restoration of cardiac activity and breathing during cardiac arrest caused by ventricular fibrillation, resistant to external electric shock:
The drug should not be administered through peripheral veins due to the risk of severe arterial hypotension and acute heart failure. It is recommended to use a central venous catheter; if it is impossible to install a catheter, the drug can be injected into the largest peripheral vein with maximum blood flow. In the future, when Cordarone is reintroduced, a central venous catheter should be used. During the period of use of the drug, dynamic monitoring of ECG and blood pressure should be carried out.
Initial dose Cordarone is 300 mg (or 5 mg/kg body weight) in 20 ml of 5% dextrose solution. The drug should be administered immediately. If necessary, an additional 150 mg (or 2.5 mg/kg body weight) of the drug is administered.
Side effects were classified by organs and systems, as well as by frequency of manifestation as follows:
- very often (≥10%);
- often (≥1%, but ≤10%);
- sometimes (≥0.1%, but ≤1%);
- rare (≥0.01%, but ≤0.1%);
- very rarely (<0.01%).
From the cardiovascular system: often - arterial hypotension or collapse (have been reported with overdose or too rapid administration), bradycardia;
From the digestive system: very often - nausea;
From the central nervous system and peripheral nervous system: very rarely - benign intracranial hypertension.
From the respiratory system: very rarely - bronchospasm and/or apnea in severe pulmonary insufficiency, acute respiratory distress syndrome.
Allergic reactions: very rarely - anaphylactic shock.
Local reactions: often - superficial phlebitis when administered into a peripheral vein, reactions at the injection site (pain, erythema, swelling, necrosis, extravasation, infiltration, inflammation, cellulite).
Others: very rarely - hair loss, increased sweating, hot flashes.
- sinus bradycardia, sinoatrial block, except in patients with an artificial pacemaker;
- SSSU with the exception of patients with an artificial pacemaker (risk of sinus node arrest);
- AV blockade of II and III degrees, intraventricular conduction disorders (blockade of two and three branches of the His bundle), with the exception of patients with an artificial pacemaker;
- hyperthyroidism;
- acute cardiovascular failure;
- severe arterial hypotension;
- simultaneous use with drugs that can cause ventricular tachycardia of the "pirouette" type: antiarrhythmic drugs, including drugs of class I A (quinidine, hydroquinidine, disopyramide) and class III (sotalol, dofetilide, ibutilide), bepridil, cisapride, sultopride, difemanil, mizolastine, vincamine for intravenous administration, erythromycin for intravenous administration, moxifloxacin, spiramycin for intravenous administration;
- pregnancy;
- lactation (breastfeeding);
- children under 3 years of age (due to the content of benzyl alcohol);
- hypersensitivity to iodine and/or amiodarone.
These contraindications do not apply to the use of the drug to restore cardiac activity and breathing during cardiac arrest caused by ventricular fibrillation, resistant to external electric shock.
Cordarone for intravenous administration is used only in a specialized hospital department under constant monitoring of ECG and blood pressure. Cordarone should be administered by infusion rather than by injection due to the risk of hemodynamic disturbances (hypotension, acute cardiovascular failure).
When using Cordarone, it is possible that existing rhythm disturbances may arise or intensify. The arrhythmogenic effect of the drug is more pronounced in patients with electrolyte imbalance or when the drug is simultaneously prescribed with antiarrhythmic drugs of other groups.
Electrolyte imbalances, especially hypokalemia, predispose to the proarrhythmogenic effects of the drug. Hypokalemia should be corrected before using Cordarone.
Several cases of interstitial pneumonia have been described with the use of injectable Cordarone. If dyspnea or dry cough occurs, either isolated or accompanied by a deterioration of the general condition, a chest x-ray should be performed.
During therapy with Cordarone in the period after surgical treatment, cases of acute respiratory distress syndrome have been described. Strict dynamic monitoring of the main indicators of the functions of the cardiovascular and respiratory systems is recommended, especially when using artificial ventilation.
During the first 24 hours after prescribing the injectable form of Cordarone, severe hepatocellular failure may develop, sometimes with death. Dynamic monitoring of liver function is recommended throughout the entire period of drug use.
IV injections of Cordarone, except in emergency cases, should be carried out only in a hospital with continuous monitoring of ECG and blood pressure.
Use of Cordarone during anesthesia:
When prescribing the drug in the preoperative period, the anesthesiologist should be notified, because long-term use of the drug can enhance the hemodynamic effects of drugs for local and general anesthesia (can increase bradycardia, arterial hypotension, reduce cardiac output, cause myocardial conduction disturbances).
The following combinations with beta-blockers (including sotalol, esmolol), verapamil, diltiazem should be prescribed with caution. Such combinations are prescribed only in cases of life-threatening ventricular arrhythmias and to restore cardiac activity and breathing during cardiac arrest caused by ventricular fibrillation resistant to external electric shock.
Impact on the ability to drive vehicles and operate machinery
The drug is intended for use only in a hospital setting; during the period of use of the drug, the patient must be under strict medical supervision.
Symptoms: sinus bradycardia, paroxysmal ventricular tachycardia, ventricular tachycardia of the "pirouette" type, liver dysfunction.
Treatment: carry out symptomatic therapy, long-term monitoring of the functions of the cardiovascular system. Amiodarone and its metabolites are not removed by dialysis.
When Cordarone and cyclosporine are co-administered, the risk of nephrotoxicity of cyclosporine increases due to an increase in its concentration in plasma and a decrease in metabolism in the liver. If it is necessary to prescribe this combination of drugs, dynamic monitoring of renal function and dose adjustment of cyclosporine during the use of amiodarone and after its discontinuation are necessary.
When Cordarone and diltiazem are co-administered (with intravenous administration of diltiazem), the risk of bradycardia and AV block increases, especially in elderly patients. If it is necessary to prescribe this combination of drugs, dynamic clinical observation and ECG monitoring are necessary.
When Cordarone is used together with halofantrine, pentamidine, lumefantrine, the risk of ventricular arrhythmias, especially ventricular tachycardia of the "pirouette" type, increases. If possible, the drug that causes tachycardia of the "pirouette" type should be discontinued. If it is necessary to use this combination, dynamic monitoring of the QT interval on an ECG should be carried out.
When Cordarone is co-administered and antipsychotics from the groups of phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), pimozide, the risk of developing ventricular arrhythmias, especially ventricular tachycardia, increases "pirouette" type.
When Cordarone is used simultaneously with anticoagulants for oral administration, the risk of bleeding increases (therefore, it is necessary to monitor the level of prothrombin, INR and adjust the dose of anticoagulants).
With the simultaneous use of Cordarone with beta-blockers, automatism and conduction disorders may develop, and the risk of developing severe bradycardia increases. If it is necessary to prescribe beta-blockers, dynamic ECG monitoring should be performed.
When Cordarone is used together with digoxin, it is possible to increase the concentration of the latter in the blood plasma due to a decrease in its clearance (therefore, it is necessary to monitor the concentration of digoxin in the blood plasma, conduct an ECG and, if necessary, change the dosage regimen).
With the simultaneous use of Cordarone with drugs that cause hypokalemia (potassium-removing diuretics, systemic corticosteroids, laxatives that stimulate intestinal motility, tetracosactide, amphotericin B), the risk of developing ventricular tachycardia increases.
When Cordarone is co-administered with lidocaine and phenytoin, an increase in the concentration of the latter in the blood plasma is observed due to a decrease in their metabolism in the liver. Clinical observation, ECG monitoring and, if necessary, dose adjustment of lidocaine and phenytoin are recommended.
With simultaneous use of Cordarone with orlistat, there is a risk of reducing the concentration of amiodarone and its active metabolite in plasma. When prescribing this combination, dynamic ECG monitoring is necessary.
When used together, the dose of simvastatin should not exceed 20 mg/day. If the therapeutic effect is not achieved at this dose, you should switch to taking another lipid-lowering drug.
Cordarone should be prescribed with caution in combination with drugs that can cause bradycardia (calcium channel blockers (verapamil), clonidine, guanfacine, mefloquine, cholinesterase inhibitors (donezepil, galantamine, rivastigmine, tacrine, ambemonium, pyridostigmine, neostigmine), pilocarpine), etc. To. when prescribing these combinations, there is a risk of excessive bradycardia due to the cumulative effect.
Cordarone is a drug with antiarrhythmic action.
Release form and composition
Cordarone is available in the following dosage forms:
- Tablets: round, off-white to off-white, with a break line on one side, chamfered and beveled from the edges to the break line on both sides, with a heart symbol above the break line and the number “200” below the line fracture (10 pcs. in blisters, 3 blisters in a cardboard box);
- Solution for intravenous administration: light yellow, transparent (in colorless glass ampoules of 3 ml, 6 ampoules in plastic blisters, 1 package in a cardboard box).
1 tablet contains:
- Active substance: amiodarone hydrochloride – 200 mg;
- Auxiliary components: corn starch, lactose monohydrate, magnesium stearate, povidone K90F, anhydrous colloidal silicon dioxide.
1 ampoule contains:
- Active substance: amiodarone hydrochloride – 150 mg;
- Auxiliary components: polysorbate 80 – 300 mg; benzyl alcohol – 60 mg; water for injection – up to 3 ml.
Indications for use
Cordarone in tablet form:
- Prevention of relapses of life-threatening ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia (therapy should be started in the hospital with careful cardiac monitoring);
- Prevention of relapses of supraventricular paroxysmal tachycardia, including 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 in cases where antiarrhythmic drugs of other classes are ineffective or there are contraindications to their use; documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome;
- Prevention of relapses of atrial flutter and atrial fibrillation (atrial fibrillation);
- Prevention of sudden arrhythmic death in patients at high risk (after a recent myocardial infarction, with clinical manifestations of chronic heart failure and reduced left ventricular ejection fraction, as well as patients with more than 10 ventricular extrasystoles per hour);
- Treatment of rhythm disturbances in patients with coronary heart disease and/or left ventricular dysfunction.
Cordarone in the form of a solution for intravenous administration:
- Relief of attacks of paroxysmal tachycardia, including relief of attacks of supraventricular paroxysmal tachycardia with a high frequency of ventricular contractions, especially in Wolff-Parkinson-White syndrome; relief of attacks of ventricular paroxysmal tachycardia; relief of persistent and paroxysmal forms of atrial fibrillation (atrial fibrillation) and atrial flutter;
- Cardiac resuscitation for cardiac arrest caused by defibrillation-resistant ventricular fibrillation.
Contraindications
- Sick sinus syndrome (sinoatrial block, sinus bradycardia) in the absence of a pacemaker - an artificial pacemaker (due to the danger of “stopping” the sinus node);
- AV blockade of II-III degree in the absence of a permanent pacemaker;
- Intraventricular conduction disturbances (two- and three-fascicle blockades) in the absence of a permanent pacemaker. In case of such conduction disorders, intravenous use of Cordarone is possible only in specialized departments under the cover of a temporary pacemaker;
- Hypomagnesemia, hypokalemia;
- Cardiogenic shock, collapse, severe arterial hypotension;
- Functional disorders of the thyroid gland (hyperthyroidism, hypothyroidism);
- Prolongation of the QT interval (acquired or congenital);
- Concomitant use with drugs that can prolong the QT interval and lead to the development of paroxysmal tachycardia, including torsade de pointes: sotalol; class I A antiarrhythmic drugs (hydroquinidine, quinidine, procainamide, disopyramide); class III antiarrhythmic drugs (ibutilide, dofetilide, bretylium tosylate); other (non-antiarrhythmic) drugs (for example, bepridil); tricyclic antidepressants; vincamine; cisapride; azoles; some neuroleptics phenothiazines (cyamemazine, chlorpromazine, fluphenazine, levomepromazine, trifluoperazine, thioridazine), benzamides (veralipride, sulpiride, amisulpride, tiapride, sultopride), butyrophenones (haloperidol, droperidol), sertindole, pimozide; macrolide antibiotics (in particular spiramycin, erythromycin when administered intravenously); pentamidine for parenteral administration; antimalarial drugs (chloroquine, quinine, halofantrine, mefloquine); mizolastine; difemanil methyl sulfate; fluoroquinolones; terfenadine, astemizole;
- Pregnancy and breastfeeding (lactation);
- Age up to 18 years (safety and effectiveness for this age group of patients have not been established);
- Hypersensitivity to the components of the drug.
Intravenous jet administration of Cordarone is contraindicated in severe respiratory failure, arterial hypotension, heart failure or cardiomyopathy (due to the possible aggravation of these conditions).
The above contraindications to the use of Cordarone during cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to defibrillation do not apply.
Cordarone should be used with caution in elderly patients (due to the high risk of developing severe bradycardia), as well as in the following diseases/conditions:
- Arterial hypotension;
- Bronchial asthma;
- Decompensated or severe heart failure (III-IV functional classes according to the NYHA classification);
- Liver failure;
- Severe respiratory failure;
- AV block of the first degree.
Directions for use and dosage
Cordarone in tablet form should be taken orally before meals, with a sufficient amount of water. The drug is used only as prescribed by a doctor.
Loading (“saturating”) dose: various saturation schemes can be used.
Inpatient treatment: the initial daily dose can vary from 600-800 mg to a maximum of 1200 mg. The daily dose should be divided into several doses. The drug is taken until the total dose is 10 g (usually 5-8 days).
Outpatient treatment: the initial daily dose is usually 600-800 mg. The daily dose should be divided into several doses. The drug is taken until the total dose is 10 g (usually 10-14 days).
Maintenance dose: may vary between patients from 100 to 400 mg per day. It is necessary to use the smallest effective dose determined by the individual therapeutic effect.
Since Cordarone has a very long half-life, it can be used every other day or with a two-day break per week.
Average therapeutic dose: single – 200 mg, daily – 400 mg.
Maximum dose: single dose – 400 mg; daily – 1200 mg.
Intravenous Cordarone is used in cases where it is necessary to achieve a rapid antiarrhythmic effect or when it is impossible to take the drug orally.
Except for emergency clinical situations, Cordarone should be used only in an intensive care unit in a hospital under constant monitoring of blood pressure and electrocardiogram (ECG).
When administered intravenously, Cordarone cannot be mixed with other drugs. Do not administer other drugs into the same infusion line at the same time.
The solution for injection is used only diluted. To dilute Cordarone, you can use only a 5% glucose solution (dextrose). Due to the characteristics of the dosage form, it is not recommended to use a concentration of infusion solution less than that obtained by diluting 2 ampoules in 0.5 l of 5% glucose solution (dextrose).
To avoid the development of reactions at the injection site, Cordarone should be administered through a central venous catheter, except in cases of cardiac resuscitation for ventricular fibrillation that is resistant to defibrillation. In this case, in the absence of central venous access, it is possible to use peripheral veins (the largest peripheral vein with maximum blood flow) to administer Cordarone.
In case of severe cardiac arrhythmias when it is impossible to take the drug orally (except for cases of cardiac resuscitation during cardiac arrest caused by ventricular fibrillation resistant to defibrillation), Cordarone can be administered intravenously through a central venous catheter or intravenously.
When administered intravenously through a central venous catheter, the loading dose is usually 5 mg/kg body weight in 250 ml of a 5% glucose solution (dextrose). If possible, the drug is administered using an electronic pump over 20-120 minutes. Within 24 hours, the procedure can be repeated up to 3 times. Depending on the clinical effect, the rate of administration of Cordarone can be adjusted. Due to the fact that the therapeutic effect of the drug gradually decreases after stopping the infusion, if it is necessary to continue therapy with an injection solution, it is recommended to switch to continuous intravenous drip administration of Cordarone.
Maintenance doses: 10-20 mg/kg per day (usually 600-800 mg, but if necessary, can be increased to 1200 mg over 24 hours) in 250 ml of 5% glucose solution (dextrose) for several days. From the first day of therapy, it is recommended to begin to gradually switch to taking Cordarone orally (3 tablets of 200 mg per day, if necessary, the dose can be increased to 4-5 tablets).
Intravenous jet administration can be carried out only in emergency cases when other types of therapy are ineffective and only in intensive care units under constant monitoring of blood pressure and ECG. Such administration is usually not recommended due to the high hemodynamic risk (collapse and sharp decrease in blood pressure).
The dose is usually 5 mg/kg body weight. Intravenous jet administration of Cordarone should be carried out for at least 3 minutes (except in cases of cardiac resuscitation for ventricular fibrillation resistant to defibrillation). Repeated administration of the drug should not be carried out earlier than 15 minutes after the first injection, even if during the first administration of the solution the contents of only one ampoule were used (due to the possibility of developing irreversible collapse). If further use of the drug is necessary, it should be administered as an infusion.
During cardiac resuscitation for cardiac arrest caused by ventricular fibrillation, which is resistant to defibrillation, intravenous bolus administration is indicated at a dose of 300 mg (5 mg/kg), diluted in 20 ml of a 5% glucose solution (dextrose). If fibrillation cannot be stopped, Cordarone can be additionally administered intravenously at a dose of 150 mg (2.5 mg/kg).
Side effects
During therapy, it is possible to develop disorders of certain body systems:
- Respiratory system: very rarely - cough, interstitial pneumonitis, shortness of breath, apnea and/or bronchospasm (in patients with severe respiratory failure, especially with bronchial asthma), acute respiratory distress syndrome (sometimes fatal);
- Cardiovascular system: often - bradycardia (usually a moderate decrease in heart rate), a decrease in blood pressure, usually transient and moderate (cases of collapse or severe arterial hypotension were observed with too rapid administration of the drug or overdose); very rarely - arrhythmogenic effect (the emergence of new arrhythmias, including ventricular tachycardia "pirouette", or aggravation of existing ones, sometimes with subsequent cardiac arrest. These effects are mainly observed when Cordarone is used together with drugs that prolong the period of repolarization of the ventricles of the heart or in case of disturbances in the content of blood electrolytes); severe bradycardia or, in rare cases, sinus node arrest, which requires cessation of therapy, especially in patients with sinus node dysfunction and/or elderly patients, flushing of the facial skin; with an unknown frequency - ventricular tachycardia of the “pirouette” type;
- Musculoskeletal system: with unknown frequency – pain in some parts of the spine (lumbar and lumbosacral);
- Immune system: very rarely - anaphylactic shock; with unknown frequency - angioedema (Quincke's edema);
- Digestive system: very rarely – nausea;
- Endocrine system: with unknown frequency – hyperthyroidism;
- Nervous system: very rarely - headache, benign intracranial hypertension (pseudotumor cerebri);
- Skin and subcutaneous tissues: very rarely - increased sweating, feeling hot; with unknown frequency – urticaria;
- Biliary tract and liver: very rarely - isolated increase in the activity of hepatic transaminases in the blood serum (usually moderate, exceeding normal values by 1.5-3 times decreases with lower doses or even spontaneously), acute liver damage (within 24 hours after administration of Cordarone) with jaundice and/or increased transaminases, including the development of liver failure, sometimes with death;
- Local reactions: often - reactions at the injection site (infection, infiltration, erythema, pain, necrosis, swelling, thrombophlebitis, pigmentation, extravasation, induration, inflammation, cellulitis, phlebitis).
Special instructions
Since the severity of side effects depends on the doses taken, therapy should be carried out in the smallest effective doses.
During the treatment period, you should avoid exposure to direct sunlight or take the necessary protective measures (wear appropriate clothing and apply sunscreen).
Before starting therapy, you need to conduct an ECG study and determine the potassium level in the blood. Hypokalemia should be corrected before using Cordarone.
Due to the fact that amiodarone can lead to the development of hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, before taking Cordarone, laboratory and clinical examination should be performed to identify thyroid dysfunction.
The appearance of a dry cough or shortness of breath may indicate pulmonary toxicity, which requires pulmonary function tests and chest x-rays.
If sinoatrial block, AV block II and III degrees, or double-bundle intraventricular block develops, therapy should be interrupted. With AV blockade of the first degree, it is necessary to intensify monitoring of the patient.
If visual acuity decreases or vision is blurred, an ophthalmological examination should be urgently performed. If neuritis or optic neuropathy develops, Cordarone should be discontinued due to the risk of developing blindness.
Before performing surgery, the anesthesiologist must be informed about the therapy being performed.
Laboratory and clinical signs of chronic liver failure when taking Cordarone orally may be minimally pronounced and reversible after discontinuation of the drug, however, there are reports of cases of death due to liver damage.
Except in emergency cases, intravenous administration of Cordarone should only be carried out in an intensive care unit with constant ECG monitoring.
It must be remembered that even slow intravenous injection of the drug can cause the development of an excessive decrease in blood pressure and circulatory collapse.
During the first 24 hours after starting to use Cordarone in the form of an injection solution, severe acute liver damage may occur with the development of liver failure (in some cases, fatal).
During therapy, it is advisable for patients with paroxysms of severe rhythm disturbances to refrain from activities that require rapid psychomotor reactions and increased concentration (driving vehicles and potentially dangerous activities).
Drug interactions
Since the simultaneous use of Cordarone with certain drugs can lead to the development of undesirable consequences (cause torsades de pointes, hypokalemia, increase the duration of the QT interval, etc.) during therapy, the use of other drugs should be agreed with a doctor.
Terms and conditions of storage
Keep out of the reach of children.
Best before date:
- Tablets – 3 years at temperatures up to 30 °C;
- Solution for intravenous administration – 2 years at temperatures up to 25 °C.
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Relieving attacks of paroxysmal tachycardia; relieving attacks of ventricular paroxysmal tachycardia; relief of attacks of 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 Cordarone solution for intravenous injection 150 mg 3 ml
Hypersensitivity to iodine, amiodarone or excipients of the drug. Sick sinus syndrome (sinus bradycardia, sinoatrial block) in the absence of an artificial pacemaker (pacemaker) (danger of “stopping” the sinus node). Atrioventricular block (II-III stage) in the absence of a permanent artificial pacemaker (pacemaker). Intraventricular conduction disturbances (two- and three-fascicle blockades) in the absence of a permanent artificial pacemaker (pacemaker). In case of such conduction disorders, intravenous use of the drug is possible only in specialized departments under the cover of a temporary pacemaker (pacemaker). Combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including torsades de pointes: antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide procainamide); class III antiarrhythmic drugs (dofetilide, ibutilide, bretylium tosylate); sotalol; bepridil; other (non-antiarrhythmic) drugs such as vincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular erythromycin when administered intravenously, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones. Congenital or acquired prolongation of the QT interval. Marked decrease in blood pressure, collapse, cardiogenic shock. Hypokalemia, hypomagnesemia. Thyroid dysfunction (hypothyroidism, hyperthyroidism). Pregnancy. Breastfeeding period. Age up to 18 years (efficacy and safety have not been established). Intravenous bolus administration is contraindicated in the case of arterial hypotension, severe respiratory failure, cardiomyopathy or heart failure (these conditions may be aggravated). All of the above contraindications do not apply to the use of the drug during cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to defibrillation. With caution: with arterial hypotension, decompensated or severe (III-IV FC CHF according to the NYHA classification) heart failure, severe respiratory failure, liver failure, bronchial asthma, in elderly patients (high risk of developing severe bradycardia), with first degree atrioventricular block . Pregnancy: Currently available clinical information is insufficient to determine the possibility or impossibility of developmental defects in the embryo when amiodarone is used in the first trimester of pregnancy. Since the fetal thyroid gland begins to bind iodine only from the 14th week of pregnancy (amenorrhea), amiodarone is not expected to affect it if it is used earlier. Excess iodine when using the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in the newborn or even to the formation of a clinically significant goiter. Due to the effect of the drug on the fetal thyroid gland, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit outweighs the risks (in case of life-threatening ventricular arrhythmias). Breastfeeding period: amiodarone is excreted into breast milk in significant quantities, so it is contraindicated during breastfeeding (therefore, during this period the drug should be discontinued or breastfeeding should be stopped).
Directions for use and dosage Cordarone solution for intravenous injection 150 mg 3 ml
The drug Cordarone, a solution 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. Other drugs should not be administered into the same infusion line as cordarone. Use only in diluted form. To dilute the drug, 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 administer an infusion solution with a concentration less than the concentration of the infusion solution obtained by diluting 2 ampoules in 500 ml of 5% dextrose (glucose). To avoid injection site reactions, the drug should be administered through a central venous catheter, except in cases of cardiac resuscitation for defibrillation-resistant ventricular fibrillation, when, in the absence of central venous access, it is possible to administer the drug into peripheral veins (usually 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 defibrillation). Intravenous drip through a central venous catheter: usually the loading dose is 5 mg/kg body weight in 250 ml of 5% dextrose (glucose) solution and is administered, if possible, using an electronic pump over 20-120 minutes. Intravenous drip administration can be repeated 2-3 times within 24 hours. The rate of drug administration 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 drug, it is recommended to switch to continuous intravenous 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 5% dextrose (glucose) solution for several days. From the first day of infusion, a gradual transition to taking the drug orally should begin (3 tablets of 200 mg per day). The dose can be increased to 4 or even 5 tablets of 200 mg per day. Intravenous bolus administration: intravenous bolus administration is usually not recommended due to hemodynamic risk (possible sharp decrease in blood pressure, collapse); Infusion administration of the drug is preferable whenever possible. Intravenous 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 body weight. With the exception of cases of cardiac resuscitation for ventricular fibrillation resistant to defibrillation, intravenous bolus administration of the drug should be carried out for at least 3 minutes. Repeated administration of the drug 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 developing irreversible collapse). If there is a need to continue administration of the drug, it should be administered as an infusion. Cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to defibrillation: intravenous bolus - the first dose is 300 mg (or 5 mg/kg of the drug) after dilution in 20 ml of a 5% dextrose (glucose) solution and administered intravenously. If fibrillation does not stop, then additional intravenous jet administration of the drug at a dose of 150 mg (or 2.5 mg/kg) is possible.
Latin name
Release form
Solution for injection.
1 ampoule with 3 ml of solution for injection contains 150 mg of amiodarone.
Package
Pharmacological action
Cordarone has antiarrhythmic and antianginal effects.
Indications
Angina pectoris, paroxysmal rhythm disturbances: supraventricular tachycardia, atrial fibrillation, sinus tachycardia, extrasystole (supraventricular and ventricular).
Contraindications
Hypersensitivity, sinus bradycardia, AV block, thyroid disease, pregnancy.
Use during pregnancy and breastfeeding
Contraindicated.
Directions for use and doses
Cordarone is administered intravenously, slowly, in a stream in a single dose of 5 mg/kg, then switched to drip infusion (from 20 minutes to 2 hours) at a dose of 150-300 mg in 250-500 ml of 5% glucose solution, maximum daily dose 1200 mg. The course is 4-5 days, then switch to oral administration
Side effects
Nausea, vomiting, constipation, bradycardia, euphoria, tremor, hypo- and hyperthyroidism, phlebitis, neuropathy, photosensitivity, headache, fatigue, allergic reactions.
Special instructions
With the exception of emergency cases, intravenous administration of Cordarone should be carried out only in the intensive care unit with constant monitoring of the ECG (due to the possibility of developing bradycardia and arrhythmogenic effects) and lowering blood pressure.
Injectable Cordarone should be administered exclusively as an infusion, since even very slow intravenous bolus administration can cause an excessive decrease in blood pressure, heart failure, or severe respiratory failure.
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 refractory 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, then Cordarone should be administered intravenously through a central venous catheter under constant monitoring of blood pressure and ECG.
Cordarone should not be mixed in the same syringe or dropper with other medications.
Due to the possibility of the development of 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, since 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) in patients who were administered Cordarone, rare cases of acute respiratory distress syndrome, sometimes fatal, have been observed (possibility of interaction with high doses of oxygen is expected) (see "Side effects"). Therefore, it is recommended to strictly monitor the condition of such patients.
During the first 24 hours after starting to use the injection form of Cordarone, severe acute liver damage may develop with the development of liver failure, sometimes with 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 restoration of cardiac activity in cardiac arrest caused by ventricular fibrillation 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 should be corrected before using Cordarone.
Before starting treatment with Cordarone, it is recommended to record an ECG and the level of potassium in the blood serum and, if possible, determine the level of thyroid hormones (T3, T4 and TSH).
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, if you switch 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. Injection Cordarone ampoules contain benzyl alcohol. Severe choking with fatal outcome has been reported in newborns after intravenous administration of solutions containing benzyl alcohol.
Drug interactions
Severe arrhythmias, such as torsades de pointes, can be caused by a number of drugs, most notably class IA and III antiarrhythmics and some antipsychotics (see below). Predisposing factors for its development may be hypokalemia, bradycardia, or congenital or acquired prolongation of the QT interval.
Contraindicated combinations (see “Contraindications”)
- With drugs that can cause torsades de pointes (when combined with amiodarone, the risk of developing potentially fatal torsades de pointes increases):
− antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide, procainamide), 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; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin for intravenous administration, spiramycin); azoles; antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones (in particular moxifloxacin).
Not recommended combinations
- With beta-blockers, calcium antagonists, slowing heart rate (verapamil, diltiazem), as there is a risk of developing disorders of automaticity (severe bradycardia) and conduction.
- With laxatives that stimulate intestinal motility, which can cause hypokalemia, which increases the risk of developing torsade de pointes. When combined with amiodarone, laxatives from other groups should be used.
Combinations requiring caution when using
- With drugs that can cause hypokalemia:
- diuretics that cause hypokalemia (in monotherapy or combination);
- amphotericin B (iv);
- systemic glucocorticosteroids;
- tetracosactide.
Increased risk of developing ventricular arrhythmias, especially ventricular tachycardia of the “pirouette” type (hypokalemia is a predisposing factor). It is necessary to monitor the level of electrolytes in the blood, if necessary, correct hypokalemia and constant clinical and electrocardiographic monitoring of the patient. In case of development of ventricular tachycardia of the “pirouette” type, antiarrhythmic drugs should not be used (ventricular pacemaking should be started, intravenous administration of magnesium salts is possible).
- With procainamide (see “Interaction. Contraindicated combinations”
Amiodarone may increase plasma concentrations of procainamide and its metabolite N-acetylprocainamide, which may increase the risk of procainamide side effects.
- With indirect anticoagulants
Amiodarone increases warfarin concentrations by inhibiting cytochrome P450 2C9. When warfarin is combined with amiodarone, the effects of the indirect anticoagulant may be enhanced, which increases the risk of bleeding. Prothrombin time (INR) should be monitored more frequently and anticoagulant doses adjusted both during treatment with amiodarone and after its discontinuation.
- With cardiac glycosides (digitalis preparations)
Possibility of disturbances in automaticity (severe bradycardia) and atrioventricular conduction. In addition, when combining digoxin with amiodarone, an increase in the concentration of digoxin in the blood plasma is possible (due to a decrease in its clearance). Therefore, when combining digoxin with amiodarone, it is necessary to determine the concentration of digoxin in the blood and monitor possible clinical and electrocardiographic manifestations of digitalis intoxication. Digoxin dosages may need to be reduced.
- With esmolol
Violations of 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 cytochrome P450 2C9, 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 flecainide
Amiodarone increases plasma concentrations of flecainide due to inhibition of cytochrome CYP 2D6. Therefore, dose adjustment of flecainide is required.
- With drugs metabolized by cytochrome P450 3A4
When amiodarone, a CYP3A4 inhibitor, 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. Such drugs are listed below.
- Cyclosporine
There may be an increase in the level 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
Combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects.
- Other drugs metabolized by CYP 3A4: 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, simvastatin and other statins metabolized by CYP 3A4 (increased risk of muscle toxicity, rhabdomyolysis, therefore the dose of simvastatin should not exceed 20 mg per day; if it is ineffective, switch to another statin that is not metabolized by CYP 3A4).
- With orlistat
Risk of decreased plasma concentrations of amiodarone and its active metabolite. Clinical and, if necessary, ECG monitoring is necessary.
- With clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine Risk of excessive bradycardia (cumulative effects).
- With cimetidine, grapefruit juice
Slowing down the metabolism of amiodarone and increasing its plasma concentrations may increase the pharmacodynamic and side effects of amiodarone.
- With drugs 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.
There have been very rare cases of severe complications from the respiratory system (acute respiratory distress syndrome in adults), sometimes fatal, that developed immediately after surgery, the occurrence of which is associated with high oxygen concentrations.
- With radioactive iodine
Amiodarone contains iodine and therefore may interfere with the absorption of radioactive iodine, which may distort the results of radioisotope studies of the thyroid gland.
- With rifampicin
Rifampicin is a strong CYP3A4 inducer and, when co-administered with amiodarone, can reduce plasma concentrations of amiodarone and desethylamiodarone.
- With St. John's wort preparations
St. John's wort is a potent inducer of CYP3A4. 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. When used simultaneously with amiodarone, the concentration of amiodarone in the blood may increase.
- 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 CYP2D6 and CYP3A4 substrate. Amiodarone inhibits CYP2D6 and may theoretically increase plasma concentrations of dectromethorphan.
Suction
After intravenous administration of amiodarone, its concentration in the blood decreases rapidly due to the drug entering the tissues. In the absence of repeated injections, amiodarone is gradually eliminated. When it is resumed intravenously or when the drug is prescribed orally, amiodarone accumulates in the tissues.
Distribution
Plasma protein binding is 95% (62% with albumin, 33.5% with beta-lipoproteins). Amiodarone has a large Vd and can accumulate in almost all tissues, especially in adipose tissue and in addition to it in the liver, lungs, spleen and cornea.
Metabolism
Amiodarone is metabolized in the liver via isoenzymes CYP3A4 and CYP2C8. Its main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. Amiodarone and its active metabolite desethylamiodarone in vitro have the ability to inhibit the isoenzymes CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and desethylamiodarone have also demonstrated the ability to inhibit certain transporters such as P-gp and organic cation transporter (POK2). In vivo, interactions of amiodarone with substrates of the isoenzymes CYP3A4, CYP2C9, CYP2D6 and P-gp were observed.
Removal
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.
Amiodarone and its metabolites are not dialyzable.
Overdose
There is no information on overdose of IV amiodarone. There is some information regarding acute overdose of amiodarone taken orally in tablet form. Several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal ventricular tachycardia of the “pirouette” type, circulatory and liver function disorders, and a pronounced decrease in blood pressure have been described.
Treatment should be symptomatic (for bradycardia - the use of beta-adrenergic agonists or the installation of a pacemaker, for ventricular tachycardia of the "pirouette" type - intravenous administration of magnesium salts, reducing cardiac pacing). Neither amiodarone nor its metabolites are removed during hemodialysis. There is no specific antidote.
Storage conditions
The drug should be stored out of the reach of children at a temperature not exceeding 25°C. Shelf life - 2 years.
Interaction with other drugs
Drugs that can cause torsade de pointes (TdP) or prolong the QT interval
Drugs that can cause torsade de pointes (TdP)
Combination therapy with drugs that can cause ventricular tachycardia of the "pirouette" type is contraindicated, because. the risk of developing potentially fatal torsade de pointes (TdP) increases.
Antiarrhythmic drugs: class I A (quinidine, hydroquinidine, disopyramide, procainamide), sotalol, bepridil;
Other (non-antiarrhythmic) drugs such as; vincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole; terfenadine
Drugs that can prolong the QT interval
Co-administration of amiodarone with drugs that can prolong the QT interval should be based on a careful assessment for each patient of the ratio of expected benefit and potential risk (the possibility of an increased risk of developing torsade de pointes); when using such combinations, it is necessary to constantly monitor the ECG of patients (for detection of QT interval prolongation), potassium and magnesium content in the blood.
Fluoroquinolones, including moxifloxacin, should be avoided in patients taking amiodarone.
Drugs that reduce heart rate or cause automaticity or conduction disturbances
Combination therapy with these drugs is not recommended.
Beta-blockers, slow calcium channel blockers that reduce heart rate (verapamil, diltiazem) can cause disturbances in automaticity (development of excessive bradycardia) and conduction.
Drugs that can cause hypokalemia
With laxatives that stimulate intestinal motility, which can cause hypokalemia, which increases the risk of developing ventricular tachycardia of the "priuet" type. When combined with amiodarone, laxatives from other groups should be used.
Combinations requiring caution when using
With diuretics that cause hypokalemia (in monotherapy or in combination with other drugs);
With systemic corticosteroids (glucocorticoids, mineralocorticoids), tetracosactide;
With amphotericin B (iv administration).
It is necessary to prevent the development of hypoglycemia, and if it occurs, restore the potassium content in the blood to normal levels, monitor the concentration of electrolytes in the blood and ECG (for possible prolongation of the QT interval), and in the event of ventricular tachycardia of the “pirouette” type, antiarrhythmic drugs should not be used (ventricular pacing should be started; intravenous administration of magnesium salts is possible).
Preparations for inhalation anesthesia
The possibility of developing the following severe complications in patients taking amiodarone while receiving anesthesia has been reported: bradycardia (resistant to atropine), arterial hypotension, conduction disturbances, decreased cardiac output.
There have been very rare cases of severe complications from the respiratory system, sometimes fatal (acute respiratory distress syndrome in adults), which developed immediately after surgery, the occurrence of which is associated with high oxygen concentrations.
Drugs that reduce heart rate (clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine
Risk of developing excessive bradycardia (cumulative effects).
Effect of amiodarone on other drugs
Amiodarone and/or its metabolite desethylamiodarone inhibit the isoenzymes CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein and may increase the systemic exposure of drugs that are their substrates. Due to the long half-life of amiodarone, this interaction may occur even several months after stopping its use.
Drugs that are P-gp substrates
Amiodarone is a P-gp inhibitor. It is expected that its combined use with drugs that are P-gp substrates will lead to increased systemic exposure of the latter.
Cardiac glycosides (digitalis preparations)
Possibility of disturbances in automaticity (severe bradycardia) and atrioventricular conduction. In addition, when combining digoxin with amiodarone, an increase in the concentration of digoxin in the blood plasma is possible (due to a decrease in its clearance). Therefore, when combining digoxin with amiodarone, it is necessary to determine the concentration of digoxin in the blood and monitor possible clinical and electrocardiographic manifestations of digitalis intoxication. Digoxin dosages may need to be reduced.
Dabigatran
Caution should be exercised when amiodarone is used concomitantly with dabigatran due to the risk of bleeding. The dose of dabigatran may need to be adjusted in accordance with the instructions in its instructions for use.
Medicines that are substrates of the CYP2C9 isoenzyme
Amiodarone increases the blood concentration of drugs that are substrates of the CYP2C9 isoenzyme, such as warfarin or phenytoin due to inhibition of cytochrome P450 2C9.
Warfarin
When warfarin is combined with amiodarone, the effects of the indirect anticoagulant may be enhanced, which increases the risk of bleeding. Prothrombin time (MHO) should be monitored more frequently and anticoagulant doses adjusted, both during treatment with amiodarone and after stopping it.
Phenytoin
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.
Medicines that are substrates of the CYP2D6 isoenzyme
Flecainide
Amiodarone increases plasma concentrations of flecainide due to inhibition of the CYP2D6 isoenzyme. Therefore, dose adjustment of flecainide is required.
Medicines that are substrates of the CYP3A4 isoenzyme
When amiodarone, an inhibitor of the CYP3A4 isoenzyme, is combined with these drugs, their plasma concentrations may increase, which may lead to increased toxicity and/or increased pharmacodynamic effects and may require a reduction in their doses. Such drugs are listed below.
Cyclosporine
The combination of cyclosporine with amiodarone may increase plasma concentrations of cyclosporine; dose adjustment is necessary.
Fentanyl
Combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects.
HMG-CoA reductase inhibitors (statins) (simvastatin, atorvastatin and lovastatin)
Increased risk of statin muscle toxicity when used concomitantly with amiodarone. The use of statins that are not metabolized by the CYP3A4 isoenzyme is recommended.
Other drugs metabolized by CYP3A4: lidocaine (risk of sinus bradycardia and neurological symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (risk of increased side effects), midazolam (risk of psychomotor effects), triazolam, dihydroergotamine, ergotamine, colchicine .
Amiodarone inhibits CYP2D6 and CYP3A4 and may theoretically increase plasma concentrations of dectromethorphan.
Clopidogrel
Clopidogrel, which is an inactive thienopyrimidine drug, is metabolized in the liver to form active metabolites. There is a possible interaction between clopidogrel and amiodarone, which may lead to a decrease in the effectiveness of clopidogrel.
Effect of other drugs on amiodarone
Inhibitors of CYP3A4 and CYP2C8 isoenzymes may have the potential to inhibit the metabolism of amiodarone and increase its concentration in the blood and, accordingly, its pharmacodynamic and side effects.
It is recommended to avoid CYP3A4 inhibitors (eg, grapefruit juice and certain drugs such as cimetidine and HIV protease inhibitors (including indinavir)) during amiodarone therapy. HIV protease inhibitors, when used concomitantly with amiodarone, may increase the concentration of amiodarone in the blood.
Inducers of the CYP3A4 isoenzyme
Rifampicin
Rifampicin is a potent inducer of the CYP3A4 isoenzyme; when used in combination with amiodarone, it can reduce plasma concentrations of amiodarone and desethylamiodarone.
Preparations of St. John's wort
St. John's wort is a potent inducer of the CYP3A4 isoenzyme. In this regard, it is theoretically possible to reduce the plasma concentration of amiodarone and reduce its effect (clinical data are not available).
Side effect
Determination of the frequency of adverse reactions: very often (≥10%); often (≥1%,
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 were observed with an overdose or too rapid administration of the drug); very rarely - arrhythmogenic effect (/there are reports of the occurrence of new arrhythmias, including ventricular tachycardia "pirouette", or aggravation of existing ones, in some cases - with subsequent cardiac arrest/, however, with amiodarone it is less pronounced than with most antiarrhythmics drugs These effects are observed mainly in cases of use of the drug Cordarone® in combination with drugs that prolong the period of repolarization of the ventricles of the heart (QTc interval) or in cases of disturbances in the level of electrolytes in the blood. Based on the available data, it is impossible to determine whether the occurrence of these rhythm disturbances is caused by the action of the drug. Cordarone®, the severity of cardiac pathology or is a consequence of treatment failure), severe bradycardia or, in exceptional cases, sinus node arrest, requiring discontinuation of treatment with amiodarone, especially in patients with sinus node dysfunction and/or elderly patients), flushing of the facial skin ; unknown frequency - ventricular tachycardia of the "pirouette" type.
From the endocrine system: frequency unknown - hyperthyroidism.
From the respiratory system: very rarely - cough, shortness of breath, interstitial pneumonitis, bronchospasm and/or apnea (in patients with severe respiratory failure, especially in patients with bronchial asthma), acute respiratory distress syndrome (sometimes fatal).
From the digestive system: very rarely - nausea.
From the liver and biliary tract: very rarely - isolated increase in the activity of hepatic transaminases in the blood serum (usually moderate, 1.5-3 times higher than normal values, decreases with dose reduction or even spontaneously), acute liver damage (within 24 hours after administration amiodarone) with increased transaminases and/or jaundice, including the development of liver failure, sometimes with death.
From the skin and subcutaneous tissues: very rarely - feeling of heat, increased sweating; frequency unknown - urticaria.
From the nervous system: very rarely - benign intracranial hypertension (pseudotumor cerebri), headache.
From the immune system: very rarely - anaphylactic shock; unknown - angioedema (Quincke's edema).
From the musculoskeletal system: frequency unknown - pain in the lumbar and lumbosacral spine.
Local reactions: often - reactions at the injection site, such as pain, erythema, swelling, necrosis, extravasation, infiltration, inflammation, induration, thrombophlebitis, phlebitis, cellulitis, infection, pigmentation.
Compound
amiodarone hydrochloride 50 mg 150 mg
Excipients: benzyl alcohol - 60 mg, polysorbate 80 - 300 mg, water for injection - up to 3 ml.
Directions for use and doses
Cordarone® for intravenous administration 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 defibrillation-resistant ventricular fibrillation, when, in the absence of central venous access, peripheral veins (the largest peripheral vein with maximum blood flow) can be used to administer the drug ).
Severe cardiac arrhythmias, in cases where it is impossible to take the drug orally (except in cases of cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to defibrillation)
Intravenous drip administration through a central venous catheter
Typically the loading dose is 5 mg/kg body weight in 250 ml of 5% dextrose (glucose) solution, administered using an electronic pump whenever possible over 20-120 minutes. Intravenous drip administration can be repeated 2-3 times within 24 hours. The rate of drug administration 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 drug Cordarone®, it is recommended to switch to continuous intravenous 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 the drug Cordarone® should begin orally (3 tablets of 200 mg/day). The dose can be increased to 4 or even 5 tablets. 200 mg/day.
Intravenous jet administration
Intravenous 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 body weight. Except in cases of cardiac resuscitation for defibrillation-resistant ventricular fibrillation, intravenous 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.
Cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to defibrillation
Intravenous jet administration
The first dose is 300 mg (or 5 mg/kg of the drug Cordarone®) after dilution in 20 ml of a 5% dextrose (glucose) solution and is administered intravenously.
If fibrillation does not stop, then additional intravenous jet administration of the drug Cordarone® at a dose of 150 mg (or 2.5 mg/kg) is possible.
Product Description
The solution for intravenous administration is transparent, light yellow in color.
With caution (Precautions)
With caution
For arterial hypotension, decompensated or severe (III-IV functional classes according to the NYHA classification) heart failure, severe respiratory failure, liver failure, bronchial asthma, in elderly patients (high risk of developing severe bradycardia), with AV blockade of the first degree.
Special instructions
With the exception of emergency cases, intravenous administration of the drug Cordarone® should be carried out only in the intensive care unit with constant monitoring of ECG (due to the possibility of developing bradycardia and arrhythmogenic effects) and blood pressure (due to the possibility of lowering blood pressure).
It should be remembered that even with slow intravenous jet administration of the drug Cordarone®, the development of an excessive decrease in blood pressure and circulatory collapse is possible.
In order to avoid reactions at the injection site, the injection form of the drug 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 defibrillation, in the absence of central venous access (no central venous catheter installed), the injectable form of the drug Cordarone® can be administered into a large peripheral vein with maximum blood flow.
If it is necessary to continue treatment with Cordarone® after cardiac resuscitation, Cordarone® should be administered intravenously through a central venous catheter under constant monitoring of blood pressure and ECG.
Cordarone® should not be mixed in the same syringe or dropper with other medications. Other drugs should not be administered into the same infusion line as Cordarone®.
Although the occurrence of arrhythmias or worsening of existing arrhythmias, sometimes fatal, has been reported, the proarrhythmogenic effect of amiodarone is weak compared to most antiarrhythmic drugs and usually occurs in the context of factors that prolong the QT interval, such as interactions with other drugs and/or disorders of electrolytes in the blood. Despite the ability of amiodarone to prolong the QT interval, amiodarone has shown little activity in inducing torsade de pointes (TdP).
Due to the possibility of developing, in very rare cases, interstitial pneumonitis after the IV administration of the drug Cordarone®, when severe shortness of breath or dry cough appears after its IV administration, 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, because interstitial pneumonitis can lead to the development of pulmonary fibrosis. However, these phenomena are mostly reversible with early withdrawal of amiodarone with or without the use of corticosteroids. Clinical manifestations usually disappear within 3-4 weeks. Recovery of the X-ray picture and lung function occurs more slowly (several months).
Following mechanical ventilation (eg, surgical interventions) in patients receiving Cordarone®, rare cases of adult acute respiratory distress syndrome, sometimes fatal, have been reported (possible interaction with high doses of oxygen). Therefore, it is recommended to strictly monitor the condition of such patients.
During the first days after starting to use the injection form of the drug Cordarone®, severe acute liver damage may develop with the development of liver failure, sometimes with a fatal outcome. Careful monitoring of liver function tests (determining transaminase activity) is recommended before starting to take the drug Cordarone® and regularly during treatment with the drug. Acute liver dysfunction (including hepatocellular failure or liver failure, sometimes fatal) and chronic liver damage may occur within the first 24 hours after IV administration of amiodarone. Therefore, treatment with amiodarone should be discontinued when transaminase activity increases to 3 times the ULN.
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.
Concomitant use with beta-blockers is not recommended; heart rate-reducing calcium channel blockers (verapamil and diltiazem); laxatives that stimulate intestinal motility, which can cause the development of hypokalemia.
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®.
Before starting treatment with Cordarone®, it is recommended to record an ECG and determine the potassium content in the blood serum and, if possible, determine the serum concentrations of thyroid hormones (T3, T4 and TSH). Side effects of the drug 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, if you switch to taking the drug 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 concentrations should be determined (using an ultrasensitive TSH test).
The safety and effectiveness of amiodarone have not been studied in children. The ampoules of the injection drug Cordarone® contain benzyl alcohol. Severe choking with fatal outcome has been reported in newborns after intravenous administration of solutions containing benzyl alcohol. Symptoms of the development of this complication are: acute development of suffocation, decreased blood pressure, bradycardia and cardiovascular collapse.
Amiodarone contains iodine and therefore can interfere with the absorption of radioactive iodine, which can distort the results of a radioisotope study of the thyroid gland, but its use does not affect the reliability of determining the content of T3, T4 and TSH in the blood plasma.
Impact on the ability to drive vehicles and operate machinery
Based on safety data, there is no evidence that amiodarone impairs the ability to drive or engage in other potentially hazardous activities. However, as a precautionary measure, it is advisable for patients with paroxysms of severe rhythm disturbances during treatment with Cordarone® to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Use during pregnancy and lactation
Pregnancy
Currently available clinical information is insufficient to determine the possibility or impossibility of developmental defects in the embryo when using amiodarone in the first trimester of pregnancy.
Since the fetal thyroid gland begins to bind iodine only from the 14th week of pregnancy (amenorrhea), amiodarone is not expected to affect it if it is used earlier. Excess iodine when using the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in the newborn or even to the formation of a clinically significant goiter.
Due to the effect of the drug on the fetal thyroid gland, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit outweighs the risks (in case of life-threatening ventricular arrhythmias).
Breastfeeding period
Amiodarone is excreted into breast milk in significant quantities, so it is contraindicated during breastfeeding (therefore, during this period the drug should be discontinued or breastfeeding should be discontinued).
Release form
solution for intravenous administration 150 mg/3 ml: amp. 6 pcs.
Expiration date from date of manufacture
Indications for use
Relief of attacks of paroxysmal tachycardia:
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 Wolff-Parkinson-White syndrome;
Relief of paroxysmal and persistent forms of atrial fibrillation (atrial fibrillation) and atrial flutter.
Cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to defibrillation.
Contraindications
Hypersensitivity to iodine, amiodarone or excipients of the drug;
SSS (sinus bradycardia, sinoatrial block) in the absence of an artificial pacemaker (pacemaker) (danger of “stopping” the sinus node);
AV blockade of II and III degrees in the absence of a permanent artificial pacemaker (pacemaker);
Intraventricular conduction disturbances (two- and three-fascicle blockades) in the absence of a permanent artificial pacemaker (pacemaker). In case of such conduction disturbances, the use of the drug Cordarone® intravenously is possible only in specialized departments under the cover of a temporary pacemaker (pacemaker);
Hypokalemia, hypomagnesemia;
Severe arterial hypotension, collapse, cardiogenic shock;
Thyroid dysfunction (hypothyroidism, hyperthyroidism);
Congenital or acquired prolongation of the QT interval;
Combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including torsades de pointes: class I A antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, procainamide); class III antiarrhythmic drugs (dofetilide, ibutilide, bretylium tosylate); sotalol; other (non-antiarrhythmic) drugs such as bepridil; vincamine; some neuroleptics phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; antibiotics of the macrolide group (in particular erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones;
Pregnancy;
Breastfeeding period;
Age up to 18 years (efficacy and safety have not been established).
Intravenous jet administration is contraindicated in the case of arterial hypotension, severe respiratory failure, cardiomyopathy or heart failure (these conditions may be aggravated).
All of the above contraindications do not apply to the use of Cordarone® during cardiac resuscitation for cardiac arrest caused by ventricular fibrillation resistant to defibrillation.
Pharmacological action
Antiarrhythmic drug. Amiodarone belongs to class III (class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action, because in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (sodium channel blockade), class IV antiarrhythmics (calcium channel blockade) and a non-competitive beta-blocker effect.
In addition to the antiarrhythmic effect, the drug has antianginal, coronary dilation, alpha and beta adrenergic blocking effects.
Antiarrhythmic action:
Increasing the duration of phase 3 of the action potential of cardiomyocytes, mainly due to blocking the ion current in potassium channels (the effect of class III antiarrhythmics according to the Williams classification);
Decreased automatism of the sinus node, leading to a decrease in heart rate;
Non-competitive blockade of α- and β-adrenergic receptors;
Slowing of sinoatrial, atrial and AV conduction, more pronounced with tachycardia;
No changes in ventricular 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 AV conduction bundles.
Other effects:
Reducing myocardial oxygen consumption due to a moderate decrease in peripheral resistance and heart rate, as well as a decrease in myocardial contractility due to the beta-adrenergic blocking effect;
Increased coronary blood flow due to a direct effect on the smooth muscle of the coronary arteries;
Preservation of cardiac output, despite a slight decrease in myocardial contractility, due to a decrease in pressure in the aorta and a decrease in peripheral vascular resistance;
Effect on the exchange of thyroid hormones: inhibition of the conversion of T3 to T4 (blockade of thyroxine-5-deiodinase) and blocking the uptake of these hormones by cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium;
Restoration of cardiac activity in cardiac arrest caused by ventricular fibrillation resistant to defibrillation.
With intravenous administration of the drug Cordarone®, its activity reaches a maximum after 15 minutes and disappears approximately 4 hours after administration.
