Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Antiarrhythmic remedy class III, has an antianginal effect.
Antiarrhythmic effect is associated with the ability to increase the duration of the action potential of cardiomyocytes and the effective refractory period of the atria, ventricles of the heart, AV-node, bundle of His, fibers Purkinje. This is accompanied by a decrease in the automatism of the sinus node, a slowing of AV conduction, a decrease in the excitability of cardiomyocytes. It is believed that the mechanism of increasing the duration of the action potential is associated with the blockade of the potassium channels (the removal of potassium ions from the cardiomyocytes decreases). Blocking inactivated "fast" sodium channels, has effects characteristic of class I antiarrhythmics. It inhibits slow (diastolic) depolarization of the membrane of the cells of the sinus node, causing bradycardia, depressing AV-conduction (effect of antiarrhythmics IV class).
The antianginal effect is due to coronary dilatory and antiadrenergic action, a decrease in myocardial oxygen demand. Has a retarding effect on the? - and? -adrenoceptors of the cardiovascular system (without complete blockade). Reduces sensitivity to hyperstimulation of the sympathetic nervous system, tone of the coronary vessels; increases coronary blood flow; reduces heart rate; increases the energy reserves of the myocardium (by increasing the content of creatine sulfate, adenosine and glycogen). Reduces OPSS and systemic blood pressure (with iv introduction).
It is believed that amiodarone may increase the level of phospholipids in tissues.
Contains iodine. Affects the metabolism of thyroid hormones, inhibits the transformation of T 3 into T 4 (blockade of thyroxine-5-deiodinase) and blocks the seizure of these hormones by cardiocytes and hepatocytes, which leads to a weakening of the stimulating effect of thyroid hormones on the myocardium (T 3 deficiency can lead to its hyperproduction and thyrotoxicosis).
When taken internally, the onset of action - from 2-3 days to 2-3 months, the duration of the action is also variable - from several weeks to several months.
After IV introduction, the maximum effect is achieved after 1-30 minutes and lasts 1-3 hours.
PHARMACOKINETICS
After oral administration, it is slowly absorbed from the digestive tract, the absorption is 20-55%. C max in blood plasma is achieved in 3-7 hours.
Due to intensive accumulation in adipose tissue and organs with a high level of blood supply (liver, lungs, spleen) has a large and variable V d and is characterized by a slow achievement of equilibrium and therapeutic concentrations in the blood plasma and to prolonged excretion. Amiodarone is determined in blood plasma up to 9 months after discontinuation of its use. High protein binding is 96% (62% with albumin, 33.5% with О±-lipoproteins).
It penetrates the GEB and the placental barrier (10-50%), excreted in breast milk (25% of the dose received by the mother).
Intensively metabolized in the liver with the formation of an active metabolite of desethylamiodarone, and also, apparently, by deiodination. With prolonged treatment, iodine concentrations can reach 60-80% of the concentration of amiodarone. It is an inhibitor of the isoenzymes CYP2C9, CYP2D6 and CYP3A4, CYP3A5, CYP3A7 in the liver.
Excretion has a two-phase character. After ingestion, T 1/2 in the initial phase is 4-21 days, in the terminal phase - 25-110 days; desiethylamidarone - an average of 61 days. As a rule, with oral oral application of T 1/2 amiodarone is 14-59 days. After intravenous administration of amiodarone T 1/2 in the terminal phase is 4-10 days. It is excreted mainly with bile through the intestine, there may be a small enterohepatic recirculation. In very small amounts, amiodarone and desethylamiodarone are excreted in the urine.
Amiodarone and its metabolites are not excreted in dialysis.
INDICATIONS
Treatment and prevention of paroxysmal rhythm disturbances: life-threatening ventricular arrhythmias (including ventricular tachycardia), prevention of ventricular fibrillation (including after cardioversion), supraventricular arrhythmias (usually with ineffectiveness or impossibility of other therapies, especially those associated with syndrome WPW), incl. paroxysm of flicker and atrial flutter; atrial and ventricular extrasystole; arrhythmias on the background of coronary insufficiency or chronic heart failure, parasystole, ventricular arrhythmias in patients with Chagas myocarditis; angina pectoris.
DOSING MODE
When administered orally for adults, the initial single dose is 200 mg. For children, the dose is 2.5-10 mg / day. Scheme and duration of treatment are set individually.
For intravenous administration (jet or drip), a single dose is 5 mg / kg, daily dose - up to 1.2 g (15 mg / kg).
SIDE EFFECT
From the cardiovascular system: sinus bradycardia (refractory to m-holinoblokatoram), AV-blockade, with prolonged use - progression of CHF, ventricular arrhythmia of the type "pirouette", strengthening of the existing arrhythmia or its occurrence, with parenteral application - a decrease in blood pressure.
From the endocrine system: the development of hypo- or hyperthyroidism.
On the part of the respiratory system: with prolonged use - cough, shortness of breath, interstitial pneumonia or alveolitis, pulmonary fibrosis, pleurisy, with parenteral use - bronchospasm, apnea (in patients with severe respiratory failure).
On the part of the digestive system: nausea, vomiting, decreased appetite, dullness or loss of taste sensations, a feeling of heaviness in the epigastrium, abdominal pain, constipation, flatulence, diarrhea; rarely - increased activity of hepatic transaminases, with prolonged use - toxic hepatitis, cholestasis, jaundice, liver cirrhosis.
From the side of the nervous system: headache, weakness, dizziness, depression, fatigue, paresthesia, auditory hallucinations, with long-term use - peripheral neuropathy, tremor, memory impairment, sleep, extrapyramidal manifestations, ataxia, optic neuritis, with parenteral application - intracranial hypertension.
From the senses: uveitis, the deposition of lipofuscin in the epithelium of the cornea (if the deposits are significant and partially fill the pupil - complaints about luminous points or shroud before the eyes in bright light), microcellular retina.
From the hemopoietic system: thrombocytopenia, hemolytic and aplastic anemia.
Dermatological reactions: skin rash, exfoliative dermatitis, photosensitivity, alopecia; rarely - a gray-blue coloration of the skin.
Local reactions: thrombophlebitis.
Other: epididymitis, myopathy, decreased potency, vasculitis, with parenteral application - fever, increased sweating.
CONTRAINDICATIONS
Sinus bradycardia, SSSU, sinoatrial blockade, AV blockade of II-III degree (without use of pacemaker), cardiogenic shock, hypokalemia, collapse, hypotension, hypothyroidism, thyrotoxicosis, interstitial lung diseases, taking MAO inhibitors, pregnancy, lactation, hypersensitivity to amiodarone and to iodine.
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation.
Amiodarone and desmethylamidarone penetrate the placental barrier, their concentrations in the fetal blood are 10% and 25% of the concentration in the mother's blood, respectively.
Amiodarone and desmethylamidarone are excreted in breast milk.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution in liver failure.
APPLICATION FOR CHILDREN
Use with caution at the age of 18 years (efficacy and safety of use not established).
APPLICATION IN ELDERLY PATIENTS
Use with caution in elderly patients (high risk of severe bradycardia).
SPECIAL INSTRUCTIONS
Use with caution in chronic heart failure, liver failure, bronchial asthma, in elderly patients (high risk of severe bradycardia), under 18 years of age (efficacy and safety of use not established).
Do not use in patients with severe respiratory failure.
Before starting the use of amiodarone, an X-ray examination of the lungs and thyroid function should be performed, if necessary, correct electrolyte disturbances.
With long-term treatment, regular monitoring of thyroid function, consultation of the oculist and X-ray examination of the lungs are necessary.
Parenteral can be used only in specialized departments of hospitals under the constant control of blood pressure, heart rate and ECG.
Patients receiving amiodarone should avoid direct exposure to sunlight.
With the cancellation of amiodarone, recurrences of cardiac rhythm disturbances are possible.
Can influence the results of the test of accumulation of radioactive iodine in the thyroid gland.
Do not use amiodarone concomitantly with quinidine, beta-blockers, calcium channel blockers, digoxin, coumarin, doxepin.
DRUG INTERACTION
The drug interaction of amiodarone with other drugs is possible even a few months after the end of its use due to prolonged T 1/2 .
With the simultaneous use of amiodarone and antiarrhythmic drugs of class I A (including disopyramide), the QT interval increases due to the additive effect on its magnitude and the risk of ventricular pirouette tachycardia increases.
With the simultaneous use of amiodarone with laxatives, which can cause hypokalemia, the risk of ventricular arrhythmia increases.
Means that cause hypokalemia, including diuretics, corticosteroids, amphotericin B (IV), tetracosactide with simultaneous use with amiodarone cause an increase in the QT interval and an increased risk of ventricular arrhythmia (including pirouette).
With the simultaneous use of funds for general anesthesia, oxygen therapy, there is a risk of bradycardia, arterial hypotension, conduction disorders, reduction of the shock volume of the heart, which, apparently, is due to additive cardiodepressive and vasodilating effects.
With simultaneous use of tricyclic antidepressants, phenothiazines, astemizole, terfenadine cause an increase in the QT interval and an increased risk of ventricular arrhythmia, especially of the pirouette type.
With the simultaneous use of warfarin, fenprokumona, acenocoumarol, the anticoagulant effect increases and the risk of bleeding increases.
With the simultaneous use of vinamine, sultopride, erythromycin (IV), pentamidine (IV, IM), the risk of ventricular arrhythmia such as pirouette increases.
With simultaneous use, an increase in the concentration of dextromethorphan in the blood plasma is possible due to a decrease in the rate of its metabolism in the liver, which is due to inhibition of the activity of the CYP2D6 isoenzyme P450 system under the influence of amiodarone and delayed excretion of dextromethorphan from the body.
With the simultaneous use of digoxin, the concentration of digoxin in the blood plasma is significantly increased due to a decrease in its clearance and, as a result, the risk of developing digitalis intoxication increases.
With the simultaneous use of diltiazem, verapamil increased negative inotropic action, bradycardia, conduction disturbance, AV blockade.
A case of increasing the concentration of amiodarone in blood plasma is described with its simultaneous application with indinavir. It is believed that ritonavir, nelfinavir, saquinavir will have similar effects.
With simultaneous application of colestyramine, the concentration of amiodarone in the blood plasma decreases due to its binding to colestyramine and a decrease in absorption from the gastrointestinal tract.
There have been reports of an increase in lidocaine concentration in the blood plasma with simultaneous use with amiodarone and the development of seizures, apparently due to inhibition of lidocaine metabolism under the influence of amiodarone.
It is believed that synergy is possible with respect to the oppressive effect on the sinus node.
With the simultaneous use of lithium carbonate may develop hypothyroidism.
With the simultaneous use of procainamide, the QT interval increases due to the additive effect on its magnitude and the risk of ventricular pirouette tachycardia. An increase in the concentration in the blood plasma of procainamide and its metabolite N-acetylprocainamide and the increase in side effects.
With the simultaneous use of propranolol, metoprolol, sotalol possible arterial hypotension, bradycardia, ventricular fibrillation, asystole.
With the simultaneous use of trazodone, a case of arrhythmia of the "pirouette" type is described.
With the simultaneous use of quinidine, the QT interval increases due to the additive effect on its magnitude and the risk of developing a ventricular pirouette tachycardia. An increase in the concentration of quinidine in the blood plasma and an increase in its side effects.
With simultaneous application, the case of enhancing the side effects of clonazepam has been described, which is apparently due to its cumulation due to the inhibition of oxidative metabolism in the liver under the influence of amiodarone.
With the simultaneous use of cisapride, the QT interval is significantly increased due to the additive effect, the risk of ventricular arrhythmia (including pirouette).
With simultaneous use increases the concentration of cyclosporine in the blood plasma, the risk of developing nephrotoxicity.
A case of pulmonary toxicity is described with simultaneous application of cyclophosphamide in high doses and amiodarone.
The concentration of amiodarone in the blood plasma increases due to the slowing of its metabolism under the influence of cimetidine and other inhibitors of microsomal liver enzymes.
It is believed that due to the inhibition of liver enzymes under the influence of amiodarone, with the participation of which the metabolism of phenytoin occurs, it is possible to increase the concentration of the latter in the blood plasma and to increase its side effects.
Due to the induction of microsomal enzymes of the liver under the influence of phenytoin, the metabolic rate of amiodarone in the liver increases and its concentration in the blood plasma decreases.
