Amiodaron-Borimed

General characteristics. Structure:

Active ingredient: 150 mg of Amiodaronum of a hydrochloride in 1 ml of solution.

Excipients: sodium acetate trihydrate, ice acetic acid, polysorbate 80, benzyl alcohol, water for injections.

Antiarrhytmic drug III of a class. Has antiarrhytmic and anti-anginal effect.

Pharmacological properties:

Pharmacodynamics. Antiarrhytmic properties: lengthening 3 phases of action potential of cardiomyocytes without change of its height or speed of rise (the III class on Vaughan Williams classification). The isolated lengthening 3 phases of action potential happens thanks to delay of potassium currents, without change of currents of sodium or calcium.

Bradikardichesky effect due to decrease in automatism of a sinus node. This effect is not eliminated with administration of atropine.

The non-competitive braking action on alpha and beta adrenoceptors, without their total block.

Delay of sinuatrial, atrialny and atrioventricular conductivity that is more expressed against the background of tachycardia.

Does not change intra ventricular conductivity.

Increases the refractory period and reduces excitability of a myocardium at the sinuatrial, atrialny and atrioventricular levels.

Slows down conductivity and extends the refractory period of additional atrioventricular ways.

Does not possess a negative inotropic effect.

Pharmacokinetics. The quantity of Amiodaronum entered parenterally in blood very quickly decreases in connection with saturation of fabrics drug and achievements of binding sites by it; action reaches a maximum in 15 minutes after introduction and disappears approximately in 4 hours.

Indications to use:

Treatment of heavy disturbances of a cordial rhythm in cases when oral administration is impossible, namely:

- disturbances of an atrial rhythm with high frequency ventricular reductions;

- the tachycardia connected with a WPW-syndrome;

- the documentary symptomatic, zhizneugrozhayushchy, leading to disability disturbances of a ventricular rhythm;

Cardiopulmonary resuscitation at the cardiac standstill caused by refractory fibrillation of a ventricle.

Route of administration and doses:

Due to the features of a dosage form of drug, it is impossible to use concentration less, than 2 500 ml ampoules, apply only isotonic solution of glucose. Not to add other drugs to infusion solution.

Amiodaronum has to be entered into the central vein, except for cases of cardiopulmonary resuscitation at a cardiac standstill when for lack of the central venous access, peripheral veins (can be used see. "Precautionary measures").

It is appointed at serious arrhythmia at which use of peroral drugs is impossible, except for cardiopulmonary resuscitation at the cardiac standstill caused by refractory fibrillation of a ventricle.

Infusion in the central vein. Initial dose: usually 5 mg/kg, in glucose solution (whenever possible – with use of an infuzomat), during of 20 minutes till 2 o'clock; it is possible to repeat injection 2-3 times within 24 hours. Brevity of effect of drug demands introduction continuation.

The supporting treatment: 10-20 mg/kg a day (on average 600-800 mg/days and to 1200 mg/days) in 250 ml of solution of glucose within several days. From the first day of infusion begin gradual transition to oral administration (3 tablets a day). The dose can be increased to 4 or even 5 tablets a day.

Infusion in a peripheral vein in the conditions of carrying out cardiopulmonary resuscitation at the cardiac standstill caused by fibrillation of ventricles refractory to an electric defibrillation.

Taking into account a route of administration and in view of a situation in which this indication arises, use of the central venous catheter is recommended if it is available; otherwise the drug can be administered in the largest peripheral vein.

The initial intravenous dose makes 300 mg (or 5 mg/kg), after dilution in 20 ml of 5% of solution of glucose. It is entered struyno.

If fibrillation is not stopped, used additional intravenous administration of 150 mg (or 2,5 mg/kg).

It is impossible to mix in one syringe with other drugs!

Features of use:

- Disturbances of electrolytic exchange, in particular hypopotassemia: it is important to take into account to a situation which can be followed by a hypopotassemia as contributing to the pro-arhythmic phenomena. The hypopotassemia has to be corrected prior to use of Amiodaronum

- Except for cases of emergency treatment, Amiodaronum in the form of solution can be applied to intravenous injections only in a hospital and at constant control (an ECG, arterial pressure).

With care apply at chronic heart failure, a liver failure, bronchial asthma, at advanced age.

Anesthesia. Before surgery of the anesthesiologist it is necessary to inform that the patient receives Amiodaronum.

Long treatment by Amiodaronum can strengthen the hemodynamic risk inherent in local or general anesthesia (can cause bradycardia, hypotension, decrease in cordial emission or disturbance of conductivity).

Combinations (see Interactions with other medicines and other forms of interaction) with beta-blockers, except a sotalol (a contraindicated combination) and an esmolola (the combination demanding extra care at use), verapamil and diltiazem, can be considered only in the context of prevention of life-threatening ventricular arrhythmias and in case of cardiopulmonary resuscitation at the cardiac standstill caused by refractory fibrillation of a ventricle.

Pregnancy and breastfeeding. Tests for animals did not reveal teratogenic action of Amiodaronum. Therefore, it is not necessary to expect malformations at the person as it is shown that defiant malformations medicinal substances show teratogenic effects at animals in correctly made experiments on two different types of animals.

In clinical practice information available now is insufficient for assessment of whether Amiodaronum causes malformations at use it in the first trimester of pregnancy. As the thyroid gland of a fruit begins to connect iodine only from 14th week of pregnancy, influence of drug on it in case of earlier use is not expected. Excess of iodine at use of drug after this period can lead to laboratory signs of a hypothyroidism at a fruit or even to a clinical craw.

Drug is contraindicated, since the second trimester of pregnancy. Amiodaronum, its metabolite and iodine are excreted in breast milk in the concentration exceeding level in maternal plasma. If mother receives treatment by this drug, feeding by a breast contraindicated in connection with danger of development of a hypothyroidism in the child.

Influence on ability to driving of motor transport and to control of mechanisms. Now there are no data that Amiodaronum influences ability to driving of motor transport and control of mechanisms.

Side effects:

Frequency of emergence of side reactions:

- very often-> 10%;

- infrequently-> 1%, <10%;

- seldom-> 0,1%, <1%;

- very seldom> 0,01%, <0,1%;

- frequency cannot be determined on the basis of the available data - <0,01% and less.

From cardiovascular system: very often: bradycardia; infrequently - the expressed bradycardia; seldom - a stop of a sinus node, were noted in certain cases, especially at elderly patients, proaritmogenny action.

From the alimentary system: often: nausea.

Local reactions in an injection site: very often: inflammatory reactions (superficial phlebitis) at introduction directly to a peripheral vein, reactions in an injection site, such as pain, erythema, hypostasis, necrosis, transudation, infiltration, inflammation, phlebitis and cellulitis are possible.

From a liver: there are messages on cases of an abnormal liver function; these cases were diagnosed on the increased level of transaminases in serum. The following was noted:

Very seldom: usually moderated and isolated increase in level of transaminases (norms are 1,5-3 times higher), the dose declines disappearing later and is even spontaneous; an acute hepatitis (several isolated cases) with increase in level of transaminases in blood and/or jaundice, sometimes - with a lethal outcome; treatment cancellation is required; chronic hepatitis at prolonged treatment (inside). The histologic picture corresponds to pseudo-alcoholic hepatitis. As the clinical and laboratory picture of a disease is very heterogeneous (the passing hepatomegalia, increase in level of transaminases by 1,5 - 5 times is a lot of), regular control of function of a liver is required. Even at the moderate increase in level of transaminases in blood which is observed after the treatment continuing over 6 months it is necessary to suspect a chronic abnormal liver function. Clinical disturbances and laboratory anomalies usually disappear after drug withdrawal. Several cases of an irreversible progression were noted.

From immune system: very seldom: acute anaphylaxis.

From a nervous system: very seldom: benign intracranial hypertensia (brain pseudoneoplasm).

From respiratory system: very seldom observed several cases acute respiratory a distress syndrome, generally interfaced to an intersticial pneumonitis, sometimes to a lethal outcome and sometimes directly after operation (the possibility of interaction with high doses of oxygen is supposed during IVL). It is necessary to consider the possibility of cancellation of Amiodaronum and expediency of purpose of corticosteroids; a bronchospasm and/or an apnoea at heavy respiratory insufficiency, in particular at patients with bronchial asthma.

From skin, hypodermic cellulose: very seldom perspiration, hair loss.

From vascular system: very often - usually moderate and passing falling of arterial pressure. Cases of heavy hypotension or circulator shock, especially after overdose or owing to too bystry introduction are described.

Very seldom: inflows.

Interaction with other medicines:

The medicines capable to cause ventricular tachycardia like "pirouette", first of all the antiarrhytmic drugs Ia and III of a class and some neuroleptics are. The hypopotassemia is the contributing factor as well as bradycardia or the inborn or acquired lengthening of an interval of QT.

Combinations are contraindicated with:

- Drugs, capable to cause ventricular tachycardia like "pirouette".

- Antiarrhytmic drugs of the class Ia (quinidine, hydroquinidine, isopyramids).

- Antiarrhytmic drugs of a class III (дофетилид, ибутилид, соталол).

- Other drugs, such as bepridit, цисаприд, difemanit, in/in ритромицин, мизоластин, in/in Vincaminum, moxifloxacin, in/in Spheromycinum.

- Sultoprid.

The risk of disturbances of a ventricular rhythm increases (tachycardias like "pirouette").

These contraindications do not belong to use of Amiodaronum for cardiopulmonary resuscitation in case of the cardiac standstill steady against an electric defibrillation.

Not recommended combinations with:

Cyclosporine. The increase in level of cyclosporine in plasma connected with decrease in metabolism of drug in a liver with possible nephrotoxic manifestations is possible. Determination of level of cyclosporine in blood, check of function of kidneys and review of a dosage during treatment by Amiodaronum and after drug withdrawal.

Diltiazem for injections. Risk of bradycardia and atrioventricular block. If the combination is inevitable, it is necessary to establish strict clinical and constant ECG control.

Verapamil for injections. Risk of bradycardia and atrioventricular block. If the combination is inevitable, it is necessary to establish strict clinical and constant ECG control. Antiparasitic drugs, capable to cause tachycardia like "pirouette" (галофантрин, pentamidine, лумефантрин). If the combination is inevitable, preliminary control of an interval of QT and monitoring of an ECG is necessary.

The neuroleptics capable to cause ventricular tachycardia like "pirouette": some fenotiazinovy neuroleptics (Chlorpromazinum, циамемазин, levomepromazinum, thioridazine, трифлуоперазин), benzamides (амисульприд, Sulpiridum, тиаприд, вералиприд), phenyl propyl ketones (Droperidolum, haloperidol), other neuroleptics (Pimozidum).

The risk of disturbances of a ventricular rhythm increases (tachycardias like "pirouette").

Methadone. The risk of disturbances of a ventricular rhythm increases (tachycardias like "pirouette"). It is recommended: ECG and clinical observation.

The combinations demanding precautions at use of Amiodaronum with:

Oral anticoagulants: strengthening of anti-coagulative effect and risk of bleeding, in connection with increase in concentration of anticoagulants in plasma. Need of more frequent control of level of a prothrombin for blood and MHO (INR), and also adaptation of doses of anticoagulants during treatment by Amiodaronum and after drug withdrawal.

Beta-blockers, except for a sotalol (a contraindicated combination) and an esmolola (the combination demanding care at use)

Disturbances of contractility, automatism and conductivity (suppression of compensatory sympathetic mechanisms). Clinical and ECG monitoring.

Beta-blockers appointed at heart failure (бисопролол, карведилол, метопролол). Disturbances of contractility and conductivity (synergy effect) with risk of development of the expressed bradycardia. The increased risk of ventricular arrhythmias, especially tachycardias like "pirouette".

Regular clinical and electrocardiographic control is necessary.

Cardiac glycosides. Automatism disturbances (excessive bradycardia) and atrioventricular conductivity (action synergism). At digoxin use, increase in its concentration in plasma (because of decrease in clearance of alkaloid).

It is necessary to carry out clinical and ECG monitoring, and also determination of level of digoxin in plasma); there can be a need for change of a dose of digoxin.

Diltiazem for oral administration. Risk of bradycardia and an atrioventricular block, especially at elderly. Clinical and ECG control.

Verapamil for oral administration. Risk of bradycardia and an atrioventricular block, especially at elderly. Clinical and ECG control.

Esmolol. Disturbances of contractility, automatism and conductivity (suppression of compensatory sympathetic mechanisms). Clinical and ECG monitoring.

Gipokaliyemichesky drugs: potassium - the removing diuretics (in monotherapy or a combination), laxatives of the stimulating character, Amphotericinum In (in/in) glucocorticoids (system), tetrakozaktidy.

The risk of disturbances of a ventricular rhythm, in particular tachycardias like "pirouette" increases (the hypopotassemia is the contributing factor). Clinical and ECG monitoring, laboratory analyses.

Lidocaine. Risk of increase in concentration of lidocaine in plasma, with probability of neurologic and cardiological side effects, in connection with decrease by Amiodaronum of metabolism of lidocaine in a liver. Clinical and ECG control, if necessary dose adjustment of lidocaine during treatment by Amiodaronum and after its cancellation.

Orlistat. Risk of decrease in concentration of Amiodaronum and its active metabolite in plasma. Clinical and, if necessary, ECG control,

Phenytoinum (and, on extrapolation, фосфенитоин). Increase in level of Phenytoinum in plasma with overdose symptoms, in particular, neurologic character (decrease in metabolism of Phenytoinum in a liver). Clinical monitoring and determination of level of Phenytoinum in plasma; whenever possible - Phenytoinum dose decline.

Simvastatin. Strengthening of risk of the side effects (depending on a dose) like a rabdomioliz (reduction of metabolism of a simvastatin in a liver). The dose of a simvastatin should not exceed 20 mg a day.

If at such dose it is not possible to reach therapeutic effect, it is necessary to pass to other statine which is not entering interactions of this kind.

Takrolimus. Increase in level of a takrolimus in blood in connection with inhibition of his metabolism by Amiodaronum. It is necessary to take measurement of level of a takrolimus in blood, control of functioning of kidneys and alignment of level of a takrolimus.

The drugs causing bradycardia: many drugs are capable to cause bradycardia. Especially it concerns the class Ia of anti-arrhythmic drugs, beta-blockers, some anti-arrhythmic drugs of a class III, some blockers of calcium channels, drugs of a digitalis, Pilocarpinum and antikholinesterazny agents. Risk of excessive bradycardia (cumulative effect).

Combinations which should be taken into account. The drugs causing bradycardia: blockers of calcium channels with bradikardichesky effect (verapamil), beta-blockers (except a sotalol), a clonidine, гуанфацин, foxglove alkaloids, мефлохин, cholinesterase inhibitors (donezepit, Galantaminum, ривастигмин, такрин, амбемониум, pyridostigmine, неостигмин), Pilocarpinum. Risk of excessive bradycardia (cumulative effects).

Incompatibility. When using material or the medical equipment from the PVC plasticized by means of 2 diethylhexylphthalates (DEGF) in the presence of injection solution of Amiodaronum DEGF can be released. For the minimum influence of DEGF it is recommended to carry out final dilution of solution before injection in the equipment which is not containing DEGF.

Contraindications:

– SSSU, a sinus bradycardia, sinuatrial blockade, except for correction cases an artificial pacemaker;

– atrioventricular block of II and III degrees, disturbances of intra ventricular conductivity (blockade of two and three legs of a ventriculonector); in these cases Amiodaronum can be intravenously used in specialized departments under cover of an artificial pacemaker (pacemaker);

– cardiogenic shock, collapse;

– the expressed arterial hypotension;

– simultaneous use with the drugs capable to cause polymorphic ventricular tachycardia like "pirouette";

– dysfunctions of a thyroid gland (hypothyroidism, hyperthyroidism);

– hypopotassemia;

– pregnancy;

– breastfeeding;

– hypersensitivity to iodine and/or Amiodaronum;

– heavy dysfunctions of lungs (intersticial pulmonary diseases);

– a cardiomyopathy or dekompensirovanny heart failure (the aggravation of symptoms of the patient is possible).

Due to the availability of benzyl alcohol intravenous administration of Amiodaronum is contraindicated at newborns, babies and children up to 3 years.

Overdose:

Symptoms: a sinus bradycardia, a cardiac standstill, Bouveret's ventricular disease, ventricular tachycardia like "pirouette", disturbances of blood circulation, an abnormal liver function, a lowering of arterial pressure.

Treatment: carry out symptomatic therapy (at bradycardia - beta адреностимуляторы or installation of a pacemaker, at tachycardia like "pirouette" - intravenous administration of salts of magnesium, urezhayushchy cardiostimulation). Amiodaronum and its metabolites are not removed at a hemodialysis and peritoneal dialysis.

Storage conditions:

In the place protected from light, at a temperature from 15 to 25 ºС. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply after expiry date.

Issue conditions:

According to the recipe

Packaging:

In ampoules on 3 ml in packaging No. 5х1, No. 5х2, No. 10.