Amiodaronum таб 0,2 g No. 30

General characteristics. Structure:

Active agent of Amiodaronum hydrochloride of 0,2 g and excipients: sugar milk, polyvinylpirrolidone middlemolecular, potato starch, talc, calcium stearate, cellulose microcrystallic. 

Description: Tablets of color, white or white with a creamy shade, ploskotsilindrichesky with risky and a facet.

Pharmacological properties:

Pharmacodynamics. Antiarrhytmic drug III of a class (repolarization inhibitor). Possesses also anti-anginal, koronarodilatiruyushchy, alpha and beta and adrenoceptor blocking, thyritropic and hypotensive action. The anti-anginal effect is caused by coronarodilator and anti-adrenergic action, reduction of need of a myocardium for oxygen.
Exerts the braking impact on alpha and beta adrenoceptors of cardiovascular system (without their total block).
Reduces sensitivity to hyper stimulation of a sympathetic nervous system, resistance of coronary vessels; increases a coronary blood stream; urezhat heart rate; raises power reserves of a myocardium (due to increase in contents creatine of sulfate, adenosine and glycogen).
Antiarrhytmic action is caused by influence on electrophysiologic processes of a myocardium; extends the action potential of cardiomyocytes, increases the effective refractory period of auricles, ventricles, an AV node, ventriculonector and Purkinye's fibers, additional ways of carrying out excitement. Blocking anaktivirovanny "bystry" natrium channels, renders the effects characteristic of antiaritmik of the I class.
Slows down slow (diastolic) depolarization of a membrane of cells of a sinus node, causing bradycardia and decrease in AV of conductivity. On the structure it is similar to thyroid hormones. Content of iodine makes about 37% of its molecular weight.
Influences exchange of thyroid hormones, inhibits transformation of T3 into T4 (blockade of a thyroxine-5-deiodinase) and blocks capture of these hormones cardiocytes and hepatocytes that leads to weakening of the stimulating influence of thyroid hormones on a myocardium (deficit of T3 can lead to its hyperproduction and a thyrotoxicosis).
The beginning of action (even when using "load" doses) – from 2-3 days to 2-3 months, varies duration of action from several weeks to one months (is defined in a blood plasma for 9 months after the termination of its reception).

Pharmacokinetics. Absorption slow and variable – 30-50%, bioavailability – 30-50%. The maximum concentration in a blood plasma is noted in 4-7 hour. Range of therapeutic plasma concentration – 1-2,5 mg/l (but when determining a dose it must be kept in mind also a clinical picture). Distribution volume – 60 l that demonstrates intensive distribution in fabric.
Has high fat solubility, in high concentration is in fatty tissue and bodies with good blood supply (concentration in fatty tissue, a liver, kidneys, a myocardium above, than in plasma – respectively, in 300, 200, 50 and 34 times). Features of pharmacokinetics of Amiodaronum cause need of use of high load doses. Gets through a blood-brain barrier and a placenta (10-50%), cosecretes with breast milk (25% of the dose received by mother). Communication with proteins of a blood plasma – 95% (62% - with albumine, 33,5% - with beta lipoproteins). It is metabolized in a liver.
The main metabolite – дезэтиламиодарон – pharmacological is active and can strengthen antiarrhytmic effect of the main connection. Perhaps, also by deiodinating (at a dose of 300 mg about 9 mg of elementary iodine are allocated). At long treatment of its concentration can reach 60-80% of concentration of Amiodaronum. Considering ability to cumulation and the big variability of pharmacokinetic parameters connected with it, data on an elimination half-life are contradictory.
Removal at oral administration proceeds in 2 phases: an initial stage – 4-21 hour, in the second phase an elimination half-life – 25-11 days. After long oral administration an average elimination half-life – 40 days (it is important at the choice of a dose as at least 1 month is necessary for stabilization of plasma concentration, and full removal can last more than 4 months).
It is removed with bile (85-95%), kidneys remove less than 1% of the accepted dose (therefore at a renal failure there is no need for change of a dosage). Neither Amiodaronum, nor its metabolites are exposed to dialysis.

Indications to use:

Amiodaronum is applied at adults:
- for treatment and the prevention of disturbances of a heart rhythm (ventricular and supraventricular tachycardia, WPW syndrome, ventricular and supraventricular premature ventricular contraction);
- for the prevention of repeated fibrillation of ventricles and auricles;
- in the rehabilitation period after a myocardial infarction if in the anamnesis there are instructions on earlier noted arrhythmia episodes.

Route of administration and doses:

Amiodaronum is accepted inside in time or after meal. The pill is taken entirely, washing down with a small amount of liquid. The dose of drug has to be adjusted depending on a condition of the patient and be defined by the doctor. The initial dose makes 600-800 mg (to 1200 mg) in the days divided into 2-3 receptions. Course of treatment of 8-15 days. If necessary increase in a dose to 1200 mg of Amiodaronum in day is possible.
After achievement of signs of saturation pass to a maintenance therapy. At the supporting treatment the smallest effective dose depending on individual reaction of the patient is applied and usually makes from 100 to 400 mg a day in 1-2 receptions. In cases when it is possible, every 5 days administration of drug does a two-day break.
For adults an average therapeutic single dose – 0,2 g, an average therapeutic daily dose – 0,4 g, the maximum single dose – 0,4 g, the maximum daily dose – 1,2 g.

Features of use:

Before therapy it is necessary to conduct X-ray inspection of lungs, to estimate function of a thyroid gland (content of hormones), a liver (transaminase). Frequency and weight of by-effects depend on a drug dose therefore it is necessary to apply the minimum effective maintenance doses.
It is necessary to be careful at treatment of patients of advanced age as bradycardia can be noted. Lengthening of an interval of QT with the advent of U tooth is possible. At emergence of a sinoauricular block, blockade of an atrioventricular node of the second or third degree and blockade of legs of a ventriculonector treatment should be interrupted.
During treatment it is regularly recommended to carry out electrocardiographic control (each 3 months), and also when developing new arrhythmias or signs of an aggravation of a basic disease. The progressing asthma and unproductive cough can be signs of damage of lungs. It is recommended to conduct X-ray inspection of a thorax and pulmonary functional trials (each 6 months and in case of development of clinical signs of diseases of lungs). Before therapy it is necessary to determine the content of electrolytes of plasma. During treatment carry regularly out by Amiodaronum control of activity of enzymes of a liver.
During treatment carry periodically out the analysis of an ECG (width of the QRS complex and duration of an interval of QT), transaminases (at increase three times or doubling in case of initially increased their activity the dose is reduced up to complete cessation of therapy). Periodic observation of the oculist is necessary (identification of considerable deposits in a cornea or development of vision disorders demands cancellation of Amiodaronum). At cancellation a recurrence of disturbances of a rhythm is possible.
Use at pregnancy and a lactation is possible only at life-threatening disturbances of a rhythm at inefficiency of other antiarrhytmic therapy (causes dysfunction of a thyroid gland of a fruit). After cancellation the pharmakodinamichesky effect remains within 10-30 days. Amiodaronum can cause dysfunction of a thyroid gland therefore it is recommended to control function of a thyroid gland before an initiation of treatment, during treatment and within several months after the treatment termination.
Contains iodine (in 200 mg – 75 mg of iodine) therefore can exert impact on results of tests of accumulation of a radioiodine in a thyroid gland. When carrying out surgical interventions to inform the anesthesiologist of administration of drug (a possibility of development acute respiratory a distress syndrome at adults directly after surgical intervention). The patients receiving drug should avoid stay in the sun because of danger of development of a photodermatosis.
It is necessary to be careful at use of drug during the general anesthesia, the risk of development of bradycardia, the expressed lowering of arterial pressure, disturbances of conductivity and reduction of a stroke output of heart is possible.
It is necessary to be careful during oxygen therapy in the postoperative period as there is a risk of development respiratory a distress – a syndrome.
Efficiency and safety of Amiodaronum at children is not established.
Impact on ability to manage the car / to work with mechanisms: At some patients drug can slow down psychomotor reactions that should be considered during the driving and work with mechanisms.

Side effects:

From a nervous system: A headache, the general weakness, dizziness, a depression, feeling of fatigue, paresthesia, auditory hallucinations, at prolonged use – peripheral neuropathy, a tremor, disturbance of memory, a dream, extrapyramidal manifestations, an ataxy, an optic neuritis.
From sense bodys: A uveitis, adjournment of lipofuscin in a cornea epithelium (subjective complaints are absent; if deposits considerable and partially fill a pupil – complaints to the shining points and a veil before eyes at bright light), retina microamotio. From cardiovascular system:
Sinus bradycardia (refractory to cholinolytics), AV blockade, at prolonged use – progressing of symptoms of heart failure, tachycardia like "pirouette", strengthening of the existing arrhythmia or its emergence.
From a metabolism: Increase in the T4 level at normal or slightly reduced T3 level, a hypothyroidism, a hyperthyroidism (drug withdrawal is required). From respiratory system:
At prolonged use – cough, short wind, intersticial pneumonia or an alveolitis, a pneumosclerosis, pleurisy.
From digestive tract: Nausea, vomiting, anorexia, obtusion or loss of flavoring feelings, heavy feeling in epigastriums, abdominal pains, a lock, a meteorism, diarrhea, at prolonged use – toxic hepatitis, a cholestasia, jaundice, cirrhosis.
Laboratory indicators: Seldom – increase in activity of "hepatic" transaminases, at prolonged use – thrombocytopenia, hemolitic and aplastic anemia.
Allergic reactions: skin rash, including exfoliative dermatitis.
Others: Myopathy, epididymite, impotence, alopecia, vasculitis, photosensitization (dermahemia, weak pigmentation of open sites of skin), lead-blue or bluish xanthopathy.

Interaction with other medicines:

Simultaneous use of drug with other antiarrhythmic means, beta adrenoblockers, some blockers of "slow" calcium channels is not allowed (verapamil), MAO inhibitors, Pentaminum (intravenously) since it can lead to development of polymorphic ventricular tachycardia (torsade de pointe). The combination with derivatives of a fenotiazin, terfenadiny and astemizoly can cause development of ventricular arrhythmias. Strengthens effect of peroral anticoagulants, nitrates, drugs of a foxglove, Phenytoinum and cyclosporine (the dose of the last needs to be korrigirovat). Colestyraminum reduces absorption, an elimination half-life and concentration of Amiodaronum in a blood plasma. Co-administration of drug and the diuretics promoting removal of potassium, glucocorticosteroids or Amphotericinum In (intravenously) can cause, because of development of a hypopotassemia, additional increase in an interval of QT that increases risk of development of ventricular arrhythmia. The concomitant use of Amiodaronum and Cimetidinum leads to delay of metabolism of Amiodaronum that causes increase in its concentration in blood serum. Amiodaronum can exert impact at a research of function of a thyroid gland, especially on the level of thyroxine and thyritropic hormone (TTG). Cardiac glycosides increase risk of development of bradycardia and oppression of atrioventricular conductivity. The drugs causing a photosensitization have the additive photosensitizing effect.

Contraindications:

Hypersensitivity to Amiodaronum and iodine, a sinus bradycardia and sinuatrial blockade, a sick sinus syndrome (in case of lack of a pacemaker), an atrioventricular block of the II-III degree, dysfunction of a thyroid gland (a hypothyroidism, a hyperthyroidism), the expressed heart failure, simultaneous treatment by drugs which can cause a polymorphic ventricular tachyarrhythmia like "pirouette" (torsade de pointe), a hypopotassemia, intersticial pulmonary diseases, reception of MAO inhibitors, pregnancy and the period of a lactation, age up to 18 years. With care to apply at a liver failure, bronchial asthma, at advanced age (high risk of development of the expressed bradycardia).
Pregnancy and period of feeding: It is not necessary to apply Amiodaronum during pregnancy (lack of data on use of drug during this period). It is not necessary to use drug during feeding as Amiodaronum has ability to get into maternal milk.

Overdose:

At emergence of signs of overdose, as a rule, happens to reduce enough a dose of drug or to temporarily stop its reception. In case of a concomitant use of a large amount of drug the lowering of arterial pressure, bradycardia, arrhythmias, an abnormal liver function, an atrioventricular block can be noted.
Treatment: a gastric lavage and purpose of absorbent carbon if drug was accepted recently. In other cases symptomatic actions. The specific antidote is not available, the hemodialysis is inefficient. At development of bradycardia it is possible to appoint atropine, a 1-adrenomimetika beta, in hard cases – cardiostimulation.

Storage conditions:

List B. To store in the dry, protected from light place. To store in the place, unavailable to children. Period of validity: 2 years. Not to use after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 0,2 g. On 10 tablets in a blister strip packaging. On 30 tablets in bank of dark glass. Each can or on 3 blister strip packagings together with the application instruction is placed in a pack from a cardboard.