Amiodaronum

General characteristics. Structure:

Active agent: Amiodaronum hydrochloride of 200 mg

Excipients: lactoses monohydrate, starch corn, povidone, silicon dioxide colloid, cellulose microcrystallic, magnesium stearate, sodium carboxymethylstarch (sodium of starch glikolit).

Pharmacological properties:

Antiarrhytmic means of a class III, possesses anti-anginal action.
The antiarrhytmic effect is connected with ability to increase duration of action potential of cardiomyocytes and the effective refractory period of auricles, ventricles of heart, an AV node, ventriculonector, Purkinye's fibers. It is followed by decrease in automatism of a sinus node, AV conductivity delay, decrease in excitability of cardiomyocytes. Believe that the mechanism of increase in duration of action potential is connected with blockade of potassium channels (removal of potassium ions from cardiomyocytes decreases). Blocking the inactivated "bystry" natrium channels, renders the effects characteristic of antiarrhytmic means of the I class. Slows down slow (diastolic) depolarization of a membrane of cells of a sinus node, causing bradycardia, AV carrying out (effect of antiaritmik of the IV class) oppresses.
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 α-and β-adrenoceptors of cardiovascular system (without their total block). Reduces sensitivity to hyper stimulation of a sympathetic nervous system, a tone of coronary vessels; increases a coronary blood stream; urezhat ChSS; raises power reserves of a myocardium (due to increase in maintenance of a kreatinsulfat, adenosine and a glycogen). Reduces the general peripheric vascular resistance and system the ABP (at in introduction).
Believe that Amiodaronum can increase the level of phospholipids in fabrics.
Contains iodine. Influences metabolism of hormones of a thyroid gland, 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).
At intake the beginning of action - from 2-3 days to 2-3 months, duration of action is also variable - from several weeks to several months.
Later in/in introductions the maximum effect is reached in 1-30 min. and proceeds 1-3 h.

Pharmacokinetics. After intake it is slowly absorbed from a GIT, absorption makes 20-55%. Cmax in a blood plasma is reached in 3-7 h.
Owing to intensive accumulation in fatty tissue and bodies with the high level of blood supply (a liver, lungs, a spleen) has big and variable Vd and it is characterized by slow achievement of equilibrium and therapeutic concentration in a blood plasma and to long removal. Amiodaronum is defined in a blood plasma up to 9 months after the termination of its use. Linkng with proteins high - 96% (62% - with albumine, 33.5% - with β-lipoproteins)))))))))).
Gets through GEB and a placental barrier (10-50%), it is allocated with breast milk (25% of the dose received by mother).
It is intensively metabolized in a liver with formation of an active metabolite of a desetilamiodaron, and also, apparently, by deiodinating. At long treatment of concentration of iodine can reach 60-80% of concentration of Amiodaronum. Is inhibitor of isoenzymes CYP2C9, CYP2D6 and CYP3A4, CYP3A5, CYP3A7 in a liver.
Removal has two-phase character. After intake of T1/2 in an initial phase makes 4-21 days, in a terminal phase - 25-110 days; a desetilamiodarona - on average 61 days. As a rule, at course oral administration of T1/2 of Amiodaronum makes 14-59 days. Later in/in introductions of Amiodaronum of T1/2 in a terminal phase makes 4-10 days. It is removed mainly with bile through intestines, small enterogepatichesky recirculation can be observed. In very small amounts Amiodaronum and десэтиламиодарон is removed with urine.
Amiodaronum and its metabolites are not removed at dialysis.

Indications to use:

Treatment and prevention of paroxysmal disturbances of a rhythm: life-threatening ventricular arrhythmias (including ventricular tachycardia), prevention of fibrillation of ventricles (including after cardioversion), supraventricular arrhythmias (as a rule, at inefficiency or impossibility of other therapy, WPW which are especially connected with a syndrome), including a paroxysm of blinking and an atrial flutter; atrial and ventricular premature ventricular contraction; arrhythmias against the background of coronary insufficiency or chronic heart failure, a parasystole, ventricular arrhythmias at patients with Shagas's myocarditis; stenocardia.

Route of administration and doses:

At intake for adults the initial single dose makes 200 mg. For children the dose makes 2.5-10 mg/days. The scheme and duration of treatment are established individually.
For in/in introductions (struyno or kapelno) the single dose makes 5 mg/kg, a daily dose - to 1.2 g (15 mg/kg).

Features of use:

With care to apply at chronic heart failure, a liver failure, bronchial asthma, at patients of advanced age (high risk of development of heavy bradycardia), aged up to 18 years (efficiency and safety of use are not established).

It is not necessary to apply at patients with heavy respiratory insufficiency.

Before use of Amiodaronum it is necessary to conduct X-ray inspection of lungs and function of a thyroid gland, if necessary, to carry out correction of electrolytic disturbances.

At prolonged treatment regular control of function of a thyroid gland, consultation of the oculist and X-ray inspection of lungs is necessary.

It is parenterally possible to apply only in specialized departments of hospitals under constant control of the ABP, ChSS and ECG.

The patients receiving Amiodaronum have to avoid direct impact of a sunlight.

At cancellation of Amiodaronum a recurrence of disturbances of a cordial rhythm is possible.

Can exert impact on test results of accumulation of a radioiodine in a thyroid gland.

It is not necessary to apply Amiodaronum along with quinidine, beta adrenoblockers, blockers of calcium channels, digoxin, coumarin, doksepiny.

Side effects:

From cardiovascular system: a sinus bradycardia (refractory to m-holinoblokatoram), AV blockade, at prolonged use - progressing HSN, ventricular arrhythmia like "pirouette", strengthening of the existing arrhythmia or its emergence, at parenteral use - decrease in the ABP.
From endocrine system: development hypo - or a hyper thyroidism.
From respiratory system: at prolonged use - cough, short wind, intersticial pneumonia or an alveolitis, a pneumosclerosis, pleurisy, at parenteral use - a bronchospasm, an apnoea (at patients with heavy respiratory insufficiency).
From the alimentary system: nausea, vomiting, a loss of appetite, obtusion or loss of flavoring feelings, heavy feeling in epigastriums, an abdominal pain, locks, a meteorism, diarrhea, it is rare - increase in activity of hepatic transaminases, at prolonged use - toxic hepatitis, a cholestasia, jaundice, cirrhosis.
From TsNS and peripheral nervous system: a headache, weakness, dizziness, a depression, feeling of fatigue, paresthesia, auditory hallucinations, at prolonged use - a peripheral neuropathy, a tremor, disturbance of memory, a dream, extrapyramidal manifestations, an ataxy, an optic neuritis, at parenteral use - intracranial hypertensia.
From sense bodys: a uveitis, adjournment of lipofuscin in a cornea epithelium (if deposits considerable and partially fill a pupil - complaints to the shining points or a veil before eyes at bright light), retina microamotio.
From system of a hemopoiesis: thrombocytopenia, hemolitic and aplastic anemia.
Dermatological reactions: skin rash, exfoliative dermatitis, photosensitivity, an alopecia, it is rare - gray-blue coloring of integuments.
Local reactions: thrombophlebitis.
Others: an epididymite, a myopathy, decrease in a potentiality, a vasculitis, at parenteral use - heat, the increased sweating.

Interaction with other medicines:

Medicinal interaction of Amiodaronum with other drugs is possible even in several months after the end of its use at the expense of a long elimination half-life.

At simultaneous use of Amiodaronum and antiarrhytmic means of a class I A (including Disopyramidum) QT interval owing to the additive action increases by its size and the risk of development of ventricular tachycardia like "pirouette" increases.

At simultaneous use of Amiodaronum with purgatives which can cause a hypopotassemia the risk of development of ventricular arrhythmia increases.

The means causing a hypopotassemia including diuretics, corticosteroids, Amphotericinum In (in/in), тетракозактид at simultaneous use with Amiodaronum cause increase in an interval of QT and increase in risk of development of ventricular arrhythmia (including the pirouette type).

At simultaneous use of means for the general anesthesia, an oxygenotherapy there is a risk of development of bradycardia, arterial hypotension, disturbances of conductivity, reduction of a stroke output of heart that, apparently, it is caused by the additive cardiodepressive and vazodilatiruyushchy effects.

At simultaneous use tricyclic antidepressants, fenotiazina, астемизол, терфенадин cause increase in an interval of QT and increase in risk of development of ventricular arrhythmia, especially the pirouette type.

At simultaneous use of warfarin, a fenprokumon, atsenokumarol anticoagulating action amplifies and the risk of development of bleedings increases.

At simultaneous use of Vincaminum, sultoprid, erythromycin (in/in), pentamidine (in/in, in oil) the risk of development of ventricular arrhythmia like "pirouette" increases.

At simultaneous use increase in concentration of dextromethorphan in a blood plasma owing to reduction of speed of his metabolism in a liver is possible that is caused by inhibition of activity of an isoenzyme of CYP2D6 of system of P450 cytochrome under the influence of Amiodaronum and delay of removal of dextromethorphan from an organism.

At simultaneous use of digoxin concentration of digoxin in a blood plasma due to decrease in its clearance and thereof, the risk of development of digitalis intoxication increases considerably increases.

At simultaneous use of diltiazem, verapamil negative inotropic effect, bradycardia, conductivity disturbance, AV blockade amplifies.

The case of increase in concentration of Amiodaronum in a blood plasma at its simultaneous use with indinaviry is described. Believe that ритонавир, нелфинавир, саквинавир will have similar effect.

At simultaneous use of Colestyraminum concentration of Amiodaronum in a blood plasma owing to its linkng with Colestyraminum and reduction of absorption from a GIT decreases.

There are messages on increase in concentration of lidocaine in a blood plasma at simultaneous use with Amiodaronum and development of spasms, apparently, owing to inhibition of metabolism of lidocaine under the influence of Amiodaronum.

Believe that a synergism concerning the oppressing action on a sinus node is possible.

At simultaneous use of lithium of a carbonate development of a hypothyroidism is possible.

At simultaneous use of procaineamide QT interval owing to the additive action increases by its size and risk of development of ventricular tachycardia like "pirouette". Increase in concentration in a blood plasma of procaineamide and its metabolite of N-atsetilprokainamida and strengthening of side effects.

At simultaneous use of propranolol, a metoprolol, sotalol arterial hypotension, bradycardia, fibrillation of ventricles, an asystolia are possible.

At simultaneous use of Trazodonum the case of development of arrhythmia like "pirouette" is described.

At simultaneous use of quinidine QT interval owing to the additive action increases by its size and risk of development of ventricular tachycardia like "pirouette". Increase in concentration of quinidine in a blood plasma and strengthening of its side effects.

At simultaneous use the case of strengthening of side effects of clonazepam is described that, apparently, is caused by its cumulation owing to inhibition of oxidizing metabolism in a liver under the influence of Amiodaronum.

At simultaneous use of a tsizaprid QT interval owing to the additive action, risk of development of ventricular arrhythmia considerably increases (including the pirouette type).

At simultaneous use concentration of cyclosporine in a blood plasma, risk of development of nephrotoxicity increases.

The case of pulmonary toxicity at simultaneous use of cyclophosphamide in high doses is described and Amiodaronum.

Concentration of Amiodaronum in a blood plasma owing to delay of his metabolism under the influence of Cimetidinum and other inhibitors of microsomal enzymes of a liver increases.

Believe that owing to inhibition under the influence of Amiodaronum of enzymes of a liver with the participation of which there is a metabolism of Phenytoinum increase in concentration of the last in a blood plasma and strengthening of its side effects is possible.

Owing to induction of microsomal enzymes of a liver under the influence of Phenytoinum the speed of metabolism of Amiodaronum in a liver increases and there is a reduction of its concentration in a blood plasma.

Contraindications:

Sinus bradycardia, SSSU, sinuatrial blockade, AV blockade of the II-III degree (without use of a pacemaker), cardiogenic shock, a hypopotassemia, a collapse, arterial hypotension, a hypothyroidism, a thyrotoxicosis, intersticial pulmonary diseases, reception of MAO inhibitors, pregnancy, the lactation period, hypersensitivity to Amiodaronum and to iodine.

Use at pregnancy and feeding by a breast
Use at pregnancy and in the period of a lactation is contraindicated.
Amiodaronum and десметиламиодарон their concentration get into fruit blood through a placental barrier, make respectively 10% and 25% of concentration in mother's blood.
Amiodaronum and десметиламиодарон is allocated with breast milk.

Use at abnormal liver functions
With care to apply at a liver failure.

Use for elderly patients
With care to apply at patients of advanced age (high risk of development of heavy bradycardia).

Use for children
With care to apply aged up to 18 years (efficiency and safety of use are not established).

Overdose:

In case of toxicity in the form of proaritmogenny effect drug is cancelled.

Symptoms: a lowering of arterial pressure, a sinus bradycardia, arrhythmias, an atrioventricular block, aggravation of the available chronic heart failure, an abnormal liver function, a cardiac standstill.

Treatment: a gastric lavage and reception of absorbent carbon if drug is accepted recently. In other cases carry out symptomatic therapy. There is no specific antidote, the hemodialysis is not effective, Amiodaronum and its metabolites are not removed at dialysis. At development of bradycardia purpose of atropine, beta адреностимуляторов or statement of a pacemaker is possible; at tachycardia like "pirouette" - intravenous administration of salts of magnesium or cardiostimulation.

Storage conditions:

To store in dry, protected from light, the place, unavailable to children, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets of 200 mg: 10, 20 and 30 pieces.