Active substance:

Amiodarone hydrochloride - 200.0 mg

Excipients:

The lactose monohydrate is 100.0 mg, the starch potato - 60.6 mg, microcrystalline cellulose - 24.0 mg, talc - 7.0 mg, povidone (polyvinylpyrrolidone) - 4.8 mg, calcium stearate - 3.6 mg.

White or white tablets with a creamy color-cylindrical colors with risk and chamfer.

Antiarrhythmic class III (repolarization inhibitor). It also has an antiagonal, coronary, alpha and beta-adren obscure and antihypertensive effect.

Blocksunactivated potassium (to a lesser extent - calcium and sodium) Channeliocyte cell membrane channels. Blocking inactivated "fast" sodium channels, has effects characteristic of antiarrhythmic media I class. Slows down slow (diastolic) depolarization of the sinus node cell membrane, causing bradycardia, inhibits atrioventricular(AV.) Conduct (effect of antiarrimics IV class).

It has the properties of a non-competitive blockator of alpha and beta-adrenoreceptors.

The antiarrhythmic effect of amiodarone is associated with its ability to output the increase in the duration of the potential of the cardiomyocytes and the effective refractory period of the atria and ventricles of the heart, the AV node, the beam of Gis, the fibers of Purkinier, which is accompanied by a decreasethe automatic system of the sinus node, slowing the AV conduction, a decrease in excitability of cardiomyocytes.

Antiangiangianthe action is due to a decrease in the need of myocardium in oxygen due to the demolition of heart rate (heart rate) and decrease in resistance coronary arteries, leading to an increase in coronary blood flow. It does not have a significant impact on systemic blood pressure (AD).

By its structure is similar to thyroid hormones. The iodine content is about 37% of its molecular weight. Affects the exchange of thyroid hormones, suppresses the transformation of thyroxine (T4) into triiodothyronine (T3)(Chiroxin-5-periodinase blockade) and blocks the capture of these hormones with cardiocytes and hepatocytes, which leads to the weakening of the stimulating effect of thyroid hormones on myocardium.

The beginning of the action (even with the use of "load" doses) - from 2-3 days to 2-3 months, the duration of action varies from several weeks to months (determined in the blood plasma for 9 months after its reception).

Suction

After taking inside slowly absorbed from gastrointestinal tract, bioavailability - 35-65%. It is found in the blood after 1 / 2-4 hours. The maximum concentration in the blood after receiving a single dose is observed after 2-10 hours. The range of therapeutic plasma concentration - 1-2.5 mg / l (but when determining the dose, it is necessary to have in a vessel and clinical picture) . Stationary concentration time(TCSS) - From one to several months (depending on individual characteristics).

Distribution

The size of the distribution is 60 l, which indicates the intense distribution in the tissues. It has a high fat solubleness, in high concentrations is in adipose tissue and organs with good blood supply (concentration in adipose tissue, liver, kidneys, myocardium is higher than in the blood plasma, respectively, 300, 200, 50 and 34 times). Features of the pharmacokinetics of amiodarone determine the need to use the drug in high load doses. Penetrates the hematosphalic barrier and the placenta (10-50%) secrets with breast milk (25% of the dose obtained by the mother). Communication with blood plasma proteins - 95% (62% - with albumin, 33.5% - with beta lipoproteins).

Metabolism

Metabolized in the liver; The main metabolite - deethelamiodamon, which has similar pharmacological propertiescan enhance the antiarrhythmic effect of the main compound. It may also be metabolized by means of a dose (at a dose of 300 mg, approximately 9 mg of elementary iodine is distinguished). With prolonged treatment of iodine concentrations, 60-80% of the concentration of amiodarone can reach. It is a carrier of organic anions, an inhibitor of p-glycoprotein and isoenzymeCYP2C9, CYP2D6.and CYP3A4, CYP3A5, CYP3A7, CYP1A1, CYP1A2, CYP2C19, CYP2A6, CYP2B6, CYP2C8in the liver.

Election

Considering the ability to cumulation and the associated large variability of pharmacokinetic parameters, the data on the half-winning period (T1 / 2) is contradictory. The removal of amiodarone after intake is carried out in 2 phases: the initial period is 4-21 hours, in the second phase T1 / 2 - 25-110 days (on average 20-100 days). After a long intake inside, the average T1 / 2 - 40 days (it is important when choosing a dose, since it is possible that at least 1 month is needed to stabilize the new plasma concentration, while complete eligibility can last more than 4 months) .

Examined through the intestines - 85-95%, the kidneys - less than 1% of the dose accepted inward (therefore, when the kidney is impaired, there is no need to change the dosage). And its metabolites are not subject to dialysis.

Prevention of recurrence of paroxysmal rhythm disorders: threatening life of ventricular arrhythmias (including ventricular tachycardia and ventricular fibrillation); reductantricular arrhythmias (including with organic heart disease, as well as in the inefficiency or inability to use other antiarrhythmic therapy); documented attacks by recurrent stable suctivativerical paroxysmal tachycardia in patients with Wolf Parkinson syndromeWhite; clear arrhythmia (atrial fibrillations) and atrial trembles.

Prevention of sudden death due to arrhythmia in patients from high-risk group: Patients after the recently suffered myocardial infarction with the number of ventricular extrasystoles more than 10 / h, with clinical signs of chronic heart failure (CHHN) and a fraction of emission of the left ventricle (LV) less than 40%.

Increased sensitivity to any of the components of the drug or iodine; Sinus node weak syndrome (sinus bradycardia and synoyatrial blockade in the absence of a pacemaker (risk of a sinus node); an atrioventricular blockade of the II-III degree, two- and three-piece blocks (in the absence of a pacemaker); hypotyroidism, hyperthyroidism; pronounced arterial hypotension; lactose intolerance, deficiency lactase, glucose-galactose maquesorption syndrome; hypokalemia, hypomagnation; interstitial disease lungs; pregnancy, breastfeeding period; The simultaneous intake of monoaminoxidase inhibitors, drugs lengthening the QT interval, congenital or acquired elongation of the QT interval; Age up to 18 years. Additionally, see the section "Interaction with other drugs".

Chronic heart failure (CHHN) (III-IV functional class according to the classification of chronic heart failure of the New York Association of Cardiologists - NYNA), an atrioventricular blockade of I degree, liver failure, bronchial asthma, elderly age (high risk of developing severe bradycardia).

If you have one of the listed diseases, before applying the drug, be sure to advice with your doctor.

The average therapeutic one-time dose is 200 mg, the average therapeutic daily dose is 400 mg. The maximum one-time dose is 400 mg, the maximum daily dose is 1200 mg.

Frequency: Very often (10% or more), often (1% or more; less than 10%), infrequent (0 1% or more; less than 1%), rarely (0.01% or more; less than 0.1% ), very rarely (less than 0.01%, including individual cases), the frequency is unknown (according to the available data it is not possible to determine the frequency).

SO cardiovascular Parties : often - moderate bradycardia (dose-dependent); Infrequently - Sinoatrial and Atrioventricular Blockade different degrees, proyrthmogenic effect; very rarely pronounced bradycardia, stopping the sinus node (in patients with sinus node dysfunction and elderly patients); The frequency is unknown - the ventricular tachycardia of the type "Piroet", the progression of symptoms of chronic heart failure ( long use).

From side digestive system: Very often - nausea, vomiting, decreased appetite, dulling or loss of taste sensations, metal taste in the mouth, sensation of gravity in epigastria, isolated increase in the activity of "liver" transaminase; Often - acute toxic hepatitis with an increase in the activity of "liver" transaminase and / or jaundice, including the development of hepatic insufficiency; Very rarely chronic liver failure.

From the respiratory system: often - interstitial oralveolar pneumonite, binding bronchiolitis with pneumonia, pleurisy, pulmonary fibrosis; Very rarely - bronchospasm in patients with severe respiratory failure (especially in patients with bronchial asthma), acute respiratory syndrome; The frequency is unknown - pulmonary bleeding.

From the body of the vision: Very often - microentes in corneal epitheliums, consisting of complex lipids, including lipofuscin (complaints about the appearance of colored halo or fuzziness of contours of objects during bright lighting); Very rarely - neuritis of the optic nerve / visual neuropathy.From the metabolism: Often - hypothyroidism, hyperthyroidism; Very rarely - the syndrome of the secretion of the antidiuretic hormone.

From the side of the skin: Very often - photosensibilization; Often - grayish or bluish skin pigmentation (with long-term use) disappears after discontinuation of the drug; Very rarely - erythema (with simultaneous radiation therapy), skin rash, exfoliative dermatitis (the tie with the reception of the drug is not established), alopecia; The frequency is unknown - urticaria.

From side nervous system: Often - tremor and other extrapyramidal disorders, sleep disorder; Infrequently - peripheral neuropathy and / or myopathy; Very rarely - cerebelchik ataxia, benign intracranial hypertension, headache.

Others: Frequency of unknown - angioedema edema, educationgranuloma, including bone marrow granulomas; Very rarely - vasculitis, epididimitis, impotence (communication with the drug intake is not established), tramobocitte, hemolytic and aplastic anemia.

With manifestation adverse Reactions It is necessary to cancel the use of the drug and consult a doctor.

If any of the side effects specified in the instructions are exacerbated or you noticed any other side effects not specified ininstructions, report this to the doctor.

Symptoms: Bradycardia AV.-block, ventricular tachycardia type "Pirouette", paroxysmal tachycardia type "Pirouette", aggravation of symptoms availableXCN, violation of the liver function, stop heart.

Treatment: stomach wash, activated carbon,symptomatic therapy (in bradycardia - beta-adrenostimuagora, or installation of the pacemaker; when tachycardia type "Pirouette" - in / in the introduction of magnesium salts, pacemaker). Hemodialysis is ineffective.

Contraindicated combinations: Risk of polymorphic ventricular tachycardia type "Piruet" (arrhythmia characterized by polymorphic complexes that change the amplitude and the direction of excitation on the ventricles relative to the insulance (electrical systole heart): antiarrhythmic agents IA class (hydrochinidin, dyspeyramide,), class III (dfethylide, ibotid ,) ,; bipridyl, phenothiazines (, shamemiazin,), benzamide (, schumatrid, verasimaride), butyrofenones (,), pimozide; tricyclic antidepressants, cisapride, macrolides (in / in,), azol, antimalarial drugs (chinin, halofantrin , Lumefantrine); Pentamidine (parenteral), dipemicanil methyl sulfate, Mizolastine, Teeferenadine, fluoroquinolones (including).

Recommended combinations: Beta adrenoblocators, blockers"slow" calcium channels (,) - the risk of violation of automatism (pronounced bradycardia) and conductivity; The laxatives that stimulate the intestinal peristalsis are the risk of the development of ventricular tachycardia type "Pirouette" against the background of hypokalemia caused by laxatives.

Combinations requiring use with caution: Diuretics causing hypocalemia, amphotericin in (intravenous), systemic glucocorticosteroids - the risk of developing rhythm ventricular roots, incl. ventricular tachycardia like "Pirouette"; - The risk of developing side effects of procainamide (makes plasma concentration of procanamide and its metabolite - N-acetyl procainamide).

Anticoagulants indirect action () - increases the concentration of warfarin (risk of bleeding) by inhibiting the Cyr2C9 isoenzysis; Heart glycosides - a violation of automatism (pronounced bradycardia) and AV conduction (increasing the concentration of digoxin).

Esmolol is a violation of the contractility, automatism and conductivity (suppression of compensatory reactions of the sympathetic nervous system).

Phoenitoine, phosphenitoine - the risk of neurological disorders (increases the concentration of phenyotine due to the inhibitory of the Syr2C9 supplement).

Flebinide - increases its concentration (due to the inhibition of the Primiment of Syr2d6).

Medicinal products, metabolizing with the participation of Cyr3A4 (Miidazolam, Triazolem, Dihydroergotamine, Argotamine, Dihydroeergotamine, Ergotamine, HMG-Coa-Reduction Inhibitors) - increases their concentration (the risk of developing their toxicity and / or enhancing pharmacodynamic effects with high doses of simvastatin increases the likelihood Development of myopathy).

Orlistat reduces the concentration of amiodarone and its active metabolite; Onidin, cholinesterase inhibitors (, tinner, ambenonia chloride, pyridomygigmine, neosygmin) - the risk of developing pronounced bradycardia.

Cimetidine, grapefruit juice slows the metabolism of amiodarone and increase its plasma concentration.

Inhalation drugs for general anesthesia are the risk of developing bradycardia (resistant to the administration of atropine), acute respiratory distress syndrome, incl. Fatal, the development of which is associated with high oxygen concentrations, risk of decline arterial pressure, cardiac output, conductivity disorders.

Radioactive - (contains in its composition) can disrupt the absorption radioactive iodinethat can distort the results of the radioisotope of the thyroid gland.

Rifampicin and the preparations of the Hypericum of the dended (strong inductors and: subfimentary SYP2A4) reduce the concentration of amiodarone in the blood plasma.

HIV inhibitors - protease (inhibitors of the isoenzyme of Cyr3A4) - can increase the plasma concentrations of amiodarone.

Medicines causing photosensitization have an additive photosensitizing effect.

Clopidogrel - it is possible to reduce its plasma concentration; Dextromethorphan (Substrate of Cyr3A4 and Sir2d6 isoenzymes) - It is possible to increase its concentration (inhibits the isoenzyme Cyr2D6). Dabigagran is an increase in its blood plasma concentration while simultaneously use with amiodaron.

Care should be taken when prescribing to patients with heart failure, liver diseases, hypokalemia, porphyria, elderly patients.

Before the start of treatment and every 6 months, during therapy, it is recommended to check the function of the thyroid gland, the activity of "liver" transaminases and to conduct an x-ray study of the lungs and counseling of the eyepiece. Control ECG needs to be shot every 3 months. It should be borne in mind that against the background of the use of amiodarone, it is possible to distort the results of determining the concentration of thyroid hormones (triiodothyronine, thyroxine, thyrotropic hormone).

At heart rate below 55, the drug should be temporarily canceled.

When applying the drug, changes are possible on the ECG: the lengthening of the intervalQt.with the possible appearance of the teethU.. With the appearance of an atrioventricular blockade of II and III degree, the synoyatrial blockade, as well as the blockade of the legs of the beam of Gis, treatment should be discontinued immediately. When canceling, recurrences of heart rhythm disorders are possible. After canceling the drug, the pharmacodynamic effect is maintained for 10-30 days. Before conducting surgical interventions, as well as oxygen therapy, it is necessary to prevent a doctor about the use of the drug, since rare cases of the development of acute respiratory distress syndrome in adult patients in the postoperative period were noted.

Inthe avoidance of the development of photosensibization patients should be avoided in the sun. The deposition of lipofuscin in the corneal epithelium decreases independently with a decrease in the dose or cancellation of amiodarone. Skin pigmentation decreases after the discontinuation of the drug and gradually (for 1-4 years) completely disappears. After discontinuation of treatment, it is observed, as a rule, spontaneous normalization of the function of the thyroid gland.

During the treatment period, it is necessary to refrain from the management of the vehicle and the lessons potentially hazardous species Activities requiring increased concentration of attention and speed of psychomotor reactions.

10 tablets in contour cellular packaging.

2, 3 contour cellular packages along with the application instructions are placed in a pack of cardboard.

In the place protected from light at a temperature not higher than 25 ° C.

Keep out of the reach of children.

Active substance: amiodarone hydrochloride in terms of 100% substance -200.00 mg; excipients: lactose monohydrate - 160.00 mg; Vidonon K-17 - 4.00 mg; calcium stearate - 2.00 mg; Potato starch - up to 400.00 mg.

White or almost white tablets, flat-cylindrical, with risky and chamfer.

Amiodaron refers to III class of antiarrhythmic drugs (the class of repolarization inhibitors) and has a unique antiarrhythmic action mechanism, since in addition to the properties of the class III antiarrimics (potassium channels), it has the effects of class I antiarrimics (blockade of sodium channels), class IV antiarrimics (calcium channel blockade ) and non-competitive beta-adrenoblocking effect.

In addition to antiarrhythmic action, it has an antiagonal, coronary-eyed, alpha and beta-adrenoblocking effects.

Antiarrhythmic properties:

-the increase in the duration of the 3rd phase of the potential of cardiomyocytes, mainly due to blocking ion current in potassium channels (effect of antiarrhythmics III classification of Williams);

-reduction of the sinus node automatism, leading to a decrease in heart rate;

-non-competitive blockade of alpha and beta adrenergic receptors;

Slowing down the synoatrial, atrial and atrioventricular conductivity, more pronounced during tachycardia;

-lack of changes in ventricular conductivity;

-an increase in refractory periods and a decrease in the excitability of the myocardium atrial and ventricles, as well as an increase in the refractory period of an atrioventricular node;

-slowing and increasing the duration of the refractory period in additional bunches of the atrocial ventricular conduct.

Other effects:

-lack of negative inotropic action when taken inside;

-reduced oxygen consumption by myocardium due to a moderate decrease in peripheral resistance and heart rate;

-an increase in the coronary blood flow due to direct impact on the smooth muscles of the coronary arteries;

-maintaining cardiac output by reducing the pressure in the aorta and reduce peripheral resistance;

-effect on the exchange of thyroid hormones: inhibition of transformationT 3 in t 4 (Chiroxin-5-periodinase blockade) and blocking the capture of these hormones with cardiocytes and hepatocytes, leading to the weakening of the stimulating effect of thyroid hormones on myocardium. Therapeutic effects Observed on average a week after the start of receiving the drug (from several days to two weeks). After the cessation of its reception is determined in the blood plasma for 9 months. It should be taken into account the possibility of preserving the pharmacodynamic effect of amiodarone within 10-30 days after its cancellation.

Bioavailability after receiving inside in different patients ranges from 30 to 80% (the average value is about 50%). After a single reception inside the amiodarone, the maximum concentrations in the blood plasma are achieved after 3-7 hours. However, the therapeutic effect is usually developing a week after the start of receiving the drug (from several days to two weeks). It is a drug with slow admission to tissue and high affinity to them. Communication with blood plasma proteins is 95% (62% with albumin, 33.5% - with beta-lipoproteins). It has a large amount of distribution. During the first days of treatment, the drug accumulates in almost all tissues, especially in adipose tissue and except for it in the liver, lungs, spleen and cornea. Metabolized in the liver with the help of isoenzymeCYP3A4.and CYP2C8.Its main metabolite - deethylamiodamon is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. and its active metabolite deethylamiodarin vitro.have the ability to inhibit the isoenzymesCYP1A1, CYP1A2, CYP2C19, CYP2D6, CYP2A6, CYP2B6and CYP2C8.Amiodaron and DeeThylamiodamon also demonstrated the ability to inhibit some conveyors such as p-glycoprotein(P-GP)and carrier of organic cations (Pok2).IN.vivothe interaction of amiodarone with substrates of isoenzyme was observedCYP3A4, CYP2C9, CYP2D6and P-GP.

The removal of amiodarone begins in a few days, and the achievement of equilibrium between the intake and removal of the drug (achieving an equilibrium state) comes from one to several months, depending on the individual characteristics of the patient. The main way is the intestine of the amiodarone. And its metabolites are not taken with hemodialysis. It has longthe half-life with large individual variability (therefore, when selecting a dose, for example, its increase or decrease, should be remembered, which is necessary at least 1 month to stabilize the new plasma concentration of amiodarone). The excavation takes place in 2 phases: the initial half-life (first phase) is 4-21 hours, the half-exploration period in the 2nd phase is 25-110 days. After a long reception inside the average half-life - 40 days. After canceling the drug, the complete removal of amiodarone from the body can continue for several months. Each dose of amiodarone (200 mg) contains 75 mg of iodine. Part of the iodine is released from the drug and is found in the urine in the form of iodide (6 mg in 24 hours at a daily dose of amiodarone 200 mg). Most of the iodine remaining in the preparation is excreted through the intestine after passing through the liver, however, with long-term reception of amiodarone, iodine concentrations can reach 60-80% of the concentrations of amiodarone in the blood. The peculiarities of the pharmacokinetics of the drug explains the use of "load" doses, which is aimed at the rapid achievement of the required level of impregnation of tissues, in which its therapeutic effect is manifested.

Pharmacokinetics with renal failure

MNN: Amiodar

Manufacturer: Open Joint-Stock Company "Borisovsky Plant of Medical Preparations" (OJSC "BSMP")

Anatomy-therapeutic-chemical classification: Amiodarone

Registration number in Kazakhstan: № RK-LS-5№016246

Registration period: 12.11.2015 - 12.11.2020

Instruction

• russian

Tradename

Amiodar

International non-proprietary title

Amiodar

Dosage form

Tablets 200 mg

Structure

One tablet contains:

active substance - amiodarone hydrochloride (in terms of 100% substance) 200 mg,

excipients: Lactoses monohydrate, starch potato, povedium, calcium stearate.

Description

White or almost white tablets, flat-cylindrical, with risky and chamfer.

F.armacotherapeutic group

Preparations for the treatment of heart disease. Antiarrhythmic drugs III classes. Amiodar.

Code ATX C01BD01.

Pharmacological properties

Pharmacokinetics

Absorption Slow and variable - 30-50%, bioavailability - 30-50%. The maximum concentration in the blood plasma is observed after 3-7 hours. The range of therapeutic plasma concentration - 1-2.5 mg / l (but when determining the dose, it is necessary to bear in mind the clinical picture). The volume of the distribution is 60 l, which indicates an intense distribution in the tissue. It has high fat-solventness, in high concentrations is in adipose tissue and organs with good blood supply (concentration in adipose tissue, liver, kidney, myocardium is higher than in plasma, respectively, 300, 200, 50 and 34 times). Features of the pharmacokinetics of amiodarone determine the need to use the drug in high load doses. Penetrates the hematorecephalic barrier and the placenta (10-50%), secrets with breast milk (25% of the dose obtained by the mother). Communication with plasma proteins is 95% (62% with albumin, 33.5% - with beta lipoproteins).

Metabolized in the liver. The main metabolit - deethylamiodamon is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. It may also be metabolized by means of a dose (at a dose of 300 mg, approximately 9 mg of elementary iodine is distinguished). With prolonged treatment of iodine concentrations, 60-80% of the concentration of amiodarone can reach. It is an inhibitor of the CYP2C9 enzyme system, CYP2D6 and CYP3A4, CYP3A5, CYP3A7 in the liver.

Given the ability to the cumulation and the associated large variability of pharmacokinetic parameters, the data on the semi-alone is contradictory. The removal of amiodarone after oral administration is carried out in 2 phases: the initial period is 4-21 hours, in the second phase half-life - 25-110 days. After a long oral administration of the average half-life - 40 days (it is important when choosing a dose, since it is possible that at least 1 month is needed to stabilize the new plasma concentration, while complete elimination can last 61 days (more 4 months).

It is excreted in bile (85-95%), the kidneys are derived less than 1% of the dose accepted inward (therefore, when the kidney is impaired, there is no need to change the dosage). Amiodaron and its metabolites are not subject to dialysis.

Pharmacodynamics

Antiarrhythmic class III (repolarization inhibitor). It also has an anti-napanese, coronary, alpha and beta-adrenoblocking and hypotensive effect.

The antianginal effect is due to the coronary industry and anti-adverergic effect, a decrease in the need of myocardium in oxygen.

It has a braking effect on the alpha and beta-adrenoreceptors of the cardiovascular system (without full blockade of their). Reduces sensitivity to hyperstimulation of the sympathetic nervous system, the tone of the coronary vessels; Increases coronary blood flow; Cause the heart rate; Increases the energy reserves of myocardium (due to an increase in the content of creatine sulfate, adenosine and glycogen).

Antiarrhythmic effect is due to the effect on electrophysiological processes in myocardium; Extensions the potential of the action of cardiomyocytes, increasing the effective refractory period of the atria, ventricles, an atrioventricular node, a beam of histnory and fibers of Purkinier, additional excitation pathways.

Blocking inactivated "fast" sodium channels, has effects characteristic of antiarrhythmic drugs I class.

Throws slow (diastolic) depolarization of the membrane of the sinus node cells, causing bradycardia, inhibits an atrioventricular conduction (the effect of the IV class antigermists).

By its structure is similar to thyroid hormones. The content of iodine is about 37% of his mol. masses. It affects the exchange of thyroid hormones, the conversion of T4 in T3 (chipoxin-5-periodinase block) and blocks the capture of these hormones with cardiocytes and hepatocytes, which leads to a weakening of the stimulating effect of thyroid hormones on myocardium.

The beginning of the action (even when using "load" doses) - from 2-3 days to 2-3 months, the duration of action varies from several weeks to months (determined in the plasma for 9 months after the reception).

Indications for use

Amiodarone therapy can be carried out only in hospitals or outpatient patrols under the supervision of the cardiologist.

For the treatment of severe arrhythmias that are not amenable to therapy with other drugs, or when other drugs cannot be appointed.

Tahiaritimia associated with Wolf Parkinson-White syndrome.

Atrial flickering and fluttering, if other drugs cannot be appointed.

Paroxysmal takhiaritimia, including atrial, atrioventricular and ventricular tachycardia, ventricular fibrillation, when other drugs cannot be appointed.

Method of application and dose

Initial treatment

The usual dispensing mode is 600 mg / day - 3 tablets per day, divided by 2-3 receptions, for 8-10 days.

In some cases, higher doses (4 or 5 tablets per day) can be applied at the beginning of treatment), but only for a short time and with electrocardiographic control.

Supporting treatment

It is necessary to determine the minimum effective dose, in accordance with the individual response, it can be from ½ tablet per day (1 tablet every day) to 2 tablets per day.

The average one-time therapeutic dose is 200 mg, the average therapeutic daily dose is 400 mg, the maximum one-time dose is 400 mg, the maximum daily dose is 1200 mg.

Side effects

Frequency: Very often (10% or more), often (1% or more; less than 10%), infrequent (0.1% or more; less than 1%), rarely (0.01% or more; less than 0.1 %), very rarely (less than 0.01%, including individual cases), the frequency is unknown (according to the available data, it is impossible to determine).

Very often (10% or more)

Nausea, vomiting, decline in appetite, dulling or loss of taste sensations, feeling of gravity in epigastrics, isolated increase in the activity of "liver" transaminase (1.5 - 3 times higher than the norm)

Microeshes in the cornea are almost always present in adults, and usually localized in the zone under the pupil and are not contraindicated to the continuation of treatment. In exceptional cases, may be accompanied by the perception of color and blinding light or leaning vision. Micro-sends in the cornea, which are formed by the lipid complex, always disappear after the cessation of treatment.

In the absence of any clinical symptoms of the distillasis, the level of "dissociated" hormone of the thyroid gland (an increase in T4 level at a normal or somewhat reduced level T3) is not a base for interrupting treatment.

Often (1% or more; less than 10%)

Moderate bradycardia (dose-dependent);

Acute toxic hepatitis with an increase in the activity of "liver" transaminase and / or jaundice, including the development of hepatic insufficiency, incl. fatal;

Interstitial or alveolar pneumonite, binding bronchiolitis with pneumonia, incl. with fatal outcome, pleurisy, pulmonary fibrosis;

With long-term use, hypothyroidism is possible, hyperthyroidism (possibly with fatal outcome, the abolition of the drug is required);

Grayish or bluish skin pigmentation (with long-term use; disappears after the discretion of the drug);

Tremor et al. Extrapyramidal symptoms, sleep disorders, incl. "Nightmarket" dreams

Infrequent (0.1% or more; less than 1%)

SA and AV blockade of various degrees, a pro-aminogenic effect (the occurrence of new or exacerbation of existing arrhythmias, incl. With a heart stop);

Violations of conductivity (synoyauricular blockade of varying degrees)

Seldom:

Peripheral neuropathy (sensory, motor, mixed) and / or myopathy

Very rarely (less than 0.01%, including individual cases)

Pronounced bradycardia, stop of the sinus node (in patients with sinus node dysfunction and elderly patients);

Chronic hepatic insufficiency (pseudo-alcoholic hepatitis, cirrhosis), incl. fatal;

Bronchospasm in patients with severe respiratory failure (especially in patients with bronchial asthma), acute respiratory syndrome, incl. with fatal outcome;

Neurry optic nerve / visual neuropathy.

Inadequate secretion syndrome ADG CHCAD / RSIADH (hyponatremia)

Erythema (with simultaneous radiation therapy), skin rash, exfoliative dermatitis (communication with the drug intake is not installed), alopecia.

Cerebelchik ataxia, benign intracranial hypertension (pseudo-turn of the brain), headache, vertigo;

Vasculitis;

Epididimitis;

Violation of the potency (communication with the reception of the drug is not established);

With long-term use of thrombocytopenia, hemolytic and aplastic anemia;

Renal failure with a moderate increase in creatinine;

The frequency is unknown (according to the available data, it is impossible to determine the frequency)

Pulmonary bleeding;

Cases of bone marrow granuloma;

Cases of angioedema edema.

Contraindications

Hypersensitivity (including to iodine);

Sinus node weakness syndrome;

Sinus bradycardia;

Synoyatrial blockade;

Atrioventricular blockade of II-III Art. (without using a pacemaker);

Cardiogenic shock;

Hypokalemia;

Collapse;

Arterial hypotension;

Hypothyroidism;

Thyrotoxicosis;

Interstitial lung diseases;

Children's and teenage age up to 18 years;

Taking monoaminoxidase inhibitors.

Two- and three perception blocks (without the use of the pacemaker);

Hypomagnation;

Hypothyroidism;

Hyperthyroidism;

Congenital or acquired lengthening of the Q-T interval;

The simultaneous reception of drugs lengthening the Q-T interval and causing paroxysmal tachycardia (including polymorphic ventricular type "Pirouette");

Pregnancy and lactation period.

Carefully: chronic insufficiency III and IV degree, AV blockade of stage I, hepatic insufficiency, bronchial asthma, elderly age (high risk of heavy bradycardia)

Medicinal interactions

Contraindicated combinations (risk of polymorphic ventricular tachycardia type "Piruet"): Class antiarrhythmic drugs 1A (CHINIDIN, hydrochinidin, dyspeyramide, procainamide), class III (dfethylide, ibetlid, broth tosylate), Satolol; buredil, vinkamine, phenothiazines (chlorpromazine, cyamemazin, levomepromazine, thiuridazine, trifluorozine, fluufenazine), benzamide (amisulpride, sulctrid, sulpiride, thiaprid, veraryprid), butyrofenons (Droperidol, Galoperidol), segindol, pimozide; tricyclic antidepressants, cisaprid, macrolides (erythromycin V / B, Spiramycin), azol, antimalarial drugs (chinin, chlorookhin, meflohin, halofantrine, lumefantrine); Pentamidine (parenteral), dipemoanyl methyl sulfate, misolastine, asthymizol, thermopenadine, fluoroquinolones (including Moxifloxacin).

Recommended combinations: beta-adrenoblays, blockers of slow calcium channels (verapamil, diltiazem) - the risk of disruption of automatic (pronounced bradycardia) and conductivity; Laxative drugs stimulating intestinal peristalsis - risk of ventricular tachycardia type "Piruet" against the background of hypokalemia caused by laxative drugs, heart glycosides - a violation of automatic (pronounced bradycardia) and AV conductivity (increasing digoxin concentration);

Combinations requiring use with caution:

Diuretics causing hypokalemia, amphotericin in (in / c), systemic glucocorticosteroids, tetracoactide - risk of rhythm violations, incl. ventricular tachycardia type "Pirouette";

Prosanamide - the risk of developing side effects of procainamide (amiodarone increases the plasma concentration of procanamide and its metabolite N-acetylpropairamide);

Anticoagulants of indirect action (warfarin) - amiodarone increases the concentration of warfarin (risk of bleeding) by inhibiting the CYP2C9 isoenzysis;

Esmolol - disruption of the contractility, automatism and conductivity (suppression of compensatory reactions of the sympathetic nervous system);

Phoenitoin, phosphenitoine - the risk of developing neurological disorders (amiodarone increases the concentration of phenytoin by inhibiting the CYP2C9 isoenzysis);

Flebinide - amiodarone increases its concentration (due to the inhibition of the CYP2D6 isoenzysis);

Medicines metabolizing with the participation of the CYP3A4 isoenzyme (cyclosporine, fentanyl, lidocaine, tacolimus, sildenafil, midazolam, triazola, dihydroeergotamine, ergotamine, statins, incl. Simvastatin - amiodarone increases their concentration (the risk of developing their toxicity and / or enhanced pharmacodynamic effects);

Orlistat reduces the concentration of amiodarone and its active metabolite; Klongidin, Guangfatzin, Holinesterase inhibitors (Donenezil, Galanamin, Rivastigmine, Torrin, Ambenonia Chloride, Pyridostigmin, Neostigmin), Pilocarpine - Risk of developing pronounced bradycardia;

Cimetidine, grapefruit juice slows the metabolism of amiodarone and increase its plasma concentration;

Drugs for inhalation anesthesia - risk of bradycardia (resistant to administration of atropine), reduction of blood pressure, conductivity disorders, reduction of cardiac output, acute respiratory distress syndrome, incl. fatal, the development of which is binding to high oxygen concentrations;

Radioactive iodine - amiodarone (contains in its composition of iodine) can disrupt the absorption of radioactive iodine, which can distort the results of the radioisotope of the thyroid gland;

Rifampicin and the preparations of the Hypericum of the reinforced (powerful inductors of the CYP3A4 isoenzyme) reduce the concentration of amiodarone in the plasma; HIV protease inhibitors (inhibitors of CYP3A4 isoenzyme) can increase the plasma concentrations of amiodarone;

Clopidogrel - it is possible to reduce its plasma concentration;

Dextromethorphan (CYP3A4 and CYP2D6 isoenzyme substrate) - it is possible to increase its concentration (amiodaron inhibits the CYP2D6 isoenzyme).

special instructions

Chronic heart failure (III-IV FC according to NYHA classification), AV blockade I Art., Hepatic insufficiency, bronchial asthma, elderly age (high risk of developing severe bradycardia).

Before starting therapy, it is necessary to carry out an ECG, X-ray study of the lungs, to estimate the function of the thyroid gland (the concentration of hormones), the liver (transaminase activity) and the concentration of electrolytes (potassium) plasma.

During the treatment period, transaminase analysis periodically monitors (with an increase of 3 times or doubling, in the case of its initially increased activity, the dose is reduced, up to the complete cessation of therapy) and the ECG (width of the QRs complex and the duration of the Qt interval). Permissible is an increase in the Qtc interval of no more than 450 ms or no more than 25% of the initial value. These changes are not a manifestation of the toxic effect of the drug, however require control to correct the dose and estimate of the possible overpritmogen action of amiodarone.

Annual X-ray study of the lungs is recommended, the study of the external respiratory function is 1 time per six months, analyzing the analysis on a thyrotropic hormone before starting treatment and then on a regular basis during treatment and a few months after the cessation of treatment. In the absence of clinical signs of the thyroid dysfunction, treatment should not be stopped. The appearance of shortness of breath or an unproductive cough may be due to toxic effect amiodarone on the lungs. Violations by the respiratory system are mainly reversible with early cancellation of amiodarone. Early cancellation of amiodarone associated with glucocorticosteroid therapy or not related to it leads to regression of violations. Clinical symptoms Usually pass within 3-4 weeks, and then slower recovery of the X-ray picture and the functions of the lungs (several months) occurs.

To prevent photosensitization development, it is recommended to avoid staying in the sun or use special sunscreen.

With the appearance of a vision of vision or reduction of visual acuity against the background of the amodarone administration, it is recommended to carry out a complete ophthalmic survey, including a filloscopy. Cases of neuropathy and / or neuritis of the optic nerve require the solution to the feasibility of the use of amiodarone.

When canceling, recurrences of rhythm disorders are possible.

Due to the presence of lactose in the preparation, it is not recommended to take to patients with congenital intolerance to galactose, lactase deficiency of Lactase, Malabsorbing glucose-galactose.

After cancellation, the pharmacodynamic effect is preserved for 10-30 days.

It contains iodine (in 200 mg - 75 mg of iodine), therefore, it can influence the results of tests for the accumulation of radioactive iodine in the thyroid gland.

When conducting surgical interventions, an anesthesiologist on the reception of the drug should be informed (the possibility of the development of acute respiratory distress syndrome in adults immediately after surgery).

In the case of simultaneous use of amiodarone and simvastatin, the Dose Simvastatin should not exceed 10 mg per day due to the potential risk of rabbomyolysis in such patients. In the case of simultaneous use of amiodarone and lovastatin, the dose of the latter should not exceed 40 mg per day. The patient should also be informed about the need to immediately appeal to the doctor in case of any unexpected muscle pain, muscle weakness.

Pregnancy and lactation

Application during pregnancy and lactation is possible only in the life of the life of rhythm disorders in the inefficiency of other antiarrhythmic therapy (causes the fetal thyroid dysfunction). Safety and efficiency of use in children is not defined.

Features of influence drug On the ability to control the vehicle or potentially hazardous mechanisms

During the treatment period, it is necessary to refrain from managing motor transport and occupying potentially hazardous activities that require increased concentrations of attention and speed of psychomotor reactions.

Overdose

Symptoms: Bradycardia, an atrioventricular blockade, decrease in blood pressure, paroxysmal tachycardia like "Pirouette", exacerbating the existing CXN, disruption of the liver function, stop the heart.

This article allows you to familiarize yourself with the instructions for the use of the drug. Amiodar. Presented reviews of site visitors - consumers of this medicine, as well as the opinions of doctors of specialists in the use of amiodarone in their practice. A big request to more actively add your reviews about the preparation: helped or did not help the medicine to get rid of the disease, which complications were observed and side effects, possibly not stated by the manufacturer in annotations. Analogs of amiodarone in the presence of available structural analogues. Use for the treatment of arrhythmias and extrasystoles in adults, children, as well as during pregnancy and breastfeeding. The composition and interaction of the drug with alcohol.

Amiodar - An antiarrhythmic agent of class 3, has an anti-infanal effect.

The antiarrhythmic effect is associated with the ability to increase the duration of the potential of the cardiomyocytes and the effective refractory period of the atrium, the ventricles of the heart, the AV of the node, the beam of Gis, the fibers of Purkinier. This is accompanied by a decrease in the automatism of the sinus node, slowing the AV conduction, a decrease in the excitability of cardiomyocytes. It is believed that the mechanism for increasing the duration of the potential of action is associated with blockade of potassium channels (reduced potassium ions from cardiomyocytes). Blocking inactivated "fast" sodium channels, has effects characteristic of class antiarrhythmic agents. Bashes slow (diastolic) depolarization of the sinus node cell membrane, causing bradycardia, oppress the AV (effect of antiarrhythmics grade 4).

The antianginal effect is due to the coronary industry and anti-adverergic effect, a decrease in the need of myocardium in oxygen. It has a braking effect on the alpha and beta-adrenoreceptors of the cardiovascular system (without full blockade of their). Reduces sensitivity to hyperstimulation of the sympathetic nervous system, the tone of the coronary vessels; Increases coronary blood flow; CIS cuts; Increases myocardial energy reserves (due to an increase in the content of creatin sulfate, adenosine and glycogen). Reduces OPS and System Hell (with intravenous administration).

It is believed that amiodarone can increase the level of phospholipids in the tissues.

Contains iodine. Affects the metabolism of the thyroid hormones, inhibits the conversion of T3 in T4 (chipoxin-5-periodinase block) and blocks the capture of these hormones with cardiocytes and hepatocytes, which leads to a weakening of the stimulating effect of thyroid hormones on myocardium (deficiency T3 may result in its hyperproduction and thyrotoxicosis) .

When taking into the beginning of action - from 2-3 days to 2-3 months, the duration of action is also variable - from several weeks to several months.

After intravenous administration The maximum effect is achieved in 1-30 minutes and continues 1-3 hours.

Structure

Amiodarone hydrochloride + excipients.

Pharmacokinetics

After receiving inside, it is slowly absorbed from the gastrointestinal tract, absorption is 20-55%. It penetrates through the hematorecephalic barrier (GEB) and a placental barrier (10-50%), is distinguished with breast milk (25% of the dose obtained by the mother). It is intensively metabolized in the liver with the formation of the active metabolite of the desethylamiodarone, as well as, apparently, by means of the event. With prolonged treatment of iodine concentrations, 60-80% of the concentration of amiodarone can reach. It is an inhibitor of CYP2C9, CYP2D6 and CYP3A4, CYP3A5, CYP3A7 in the liver. It is displayed mainly with bile through the intestines, a small enterogeptic recycling can be observed. In very small amounts of amiodarone and pre-ethyllamiodamon, it is excreted in urine. Amiodaron and its metabolites are not displayed in dialysis.

Indications

• threatening life of ventricular arrhythmias (including ventricular tachycardia);
• prevention of ventricular fibrillation (incl. after cardioversion);
• supported arrhythmias (as a rule, with ineffectiveness or impossibility of other therapy, especially related to WPW syndrome), incl. Paroxism of the flicker and fluttering atrial;
• atrial and ventricular extrasystole;
• arrhythmias against the background of coronary insufficiency or chronic heart failure;
• parasistolia;
• stomatricular arrhythmias in patients with myocarditis of Shagas;
• angina.

Forms of release

Tablets 200 mg.

The solution for intravenous administration is 5% (injections in ampoules for injection).

Instructions for use and dosage

When taking inside for adults, the initial one-time dose is 200 mg. For children, the dose is 2.5-10 mg per day. The diagram and the duration of treatment are established individually.

For intravenous administration (inkjet or drip (in the form of a dropper)), one-time dose is 5 mg / kg, a daily dose - up to 1.2 g (15 mg / kg).

Side effect

• sinus bradycardia (refractory to m-cholinoblocators);
• AV blockade;
• progression of hsn;
• ventricular arrhythmia type "Pirouette";
• strengthening the existing arrhythmia or its occurrence;
• reduction of blood pressure;
• development of hypo- or hyperthyroidism;
• cough;
• dyspnea;
• interstitial pneumonia or alveolit;
• fibrosis of the lungs;
• pleurisy;
• bronchospasm;
• apnea (in patients with severe respiratory failure);
• nausea, vomiting;
• decline in appetite;
• dulling or loss of taste sensations;
• feeling of gravity in epigastrics;
• abdominal pain;
• constipation, diarrhea;
• flatulence;
• toxic hepatitis;
• cholestasis;
• jaundice;
• cirrhosis of the liver;
• headache;
• weakness;
• dizziness;
• depression;
• feeling of fatigue;
• paresthesia;
• hearing hallucinations;
• peripheral neuropathy;
• tremor;
• memory violation, sleep;
• neuritis optic nerve;
• intracranial hypertension;
• will take away;
• the deposition of lipofuscin in the corneal epitheliums (if there is significant deposits and partially fill the pupil - complaints about glowing points or a veil before your eyes during bright light);
• retina microsilate;
• thrombocytopenia;
• hemolytic and aplastic anemia;
• skin rash;
• exfoliative dermatitis;
• photosensitivity;
• alopecia;
• gray-blue staining of skin;
• thrombophlebitis;
• epididimitis;
• myopathy;
• reduction potency;
• vasculitis;
• increased sweating.

Contraindications

• sinus bradycardia;
• sinus node weakness syndrome (SCC);
• synoyatrial blockade;
• AV blockade 2-3 degrees (without using a pacemaker);
• cardiogenic shock;
• hypokalemia;
• collapse;
• arterial hypotension;
• hypothyroidism;
• thyrotoxicosis;
• interstitial lung diseases;
• reception of Mao inhibitors;
• pregnancy;
• lactation period;
• increased sensitivity to amiodarone and iodine.

Application in pregnancy and breastfeeding

Application is contraindicated during pregnancy and during lactation.

Amiodaron and desmethylamiodamyron are penetrated through the placental barrier, their concentrations in the blood of the fetus are 10% and 25% of the concentration in the blood of the mother.

Amyodaron and desmethylamiodrone stand out with breast milk.

Application in children

Caution to apply under the age of 18 (efficiency and safety of applications are not established).

Application in elderly patients

Caution to apply in elderly patients (high risk of heavy bradycardia).

special instructions

Do not apply in patients with severe respiratory failure.

Before starting the use of amiodarone, a radiographic study of the lungs and the functions of the thyroid gland should be carried out, if necessary, to correct electrolyte disorders.

With long-term treatment, regular control of the function of the thyroid gland is needed, the counseling of the eyepiece and the X-ray study of the lungs.

Parenterally can be used only in specialized departments under constant control of Hell, CSS and ECG.

Patients receiving amiodarone should avoid direct exposure to sunlight.

With the abolition of amiodarone, recurrences of heart rate disorders are possible.

It can influence the results of the test of the accumulation of radioactive iodine in the thyroid gland.

It should not be used amiodaron simultaneously with quinidine, beta-adrenobloclars, calcium channels, digoxin, kumarin, dofepine.

Medicinal interaction

Medicinal interaction of amiodarone with other drugs is possible even a few months after its application due to the long period of half-life.

With the simultaneous use of amiodarone and antiarrhythmic agents of class 1 A (including dyspeyramide), the Qt interval increases due to an additive action on its magnitude and increases the risk of development of ventricular tachycardia like "Pirouette".

With the simultaneous use of amiodarone with laxative means, which can cause hypokalemia, the risk of ventricular arrhythmia is increased.

Hypocalemia, including diuretics, corticosteroids, amphotericin in (in / c), tetracocalidide, with simultaneous use with amiodaron, cause an increase in Qt interval and raising the risk of development of ventricular arrhythmias (including the "Pirouette" type).

With the simultaneous use of funds for general anesthesia, oxygen therapy arises the risk of bradycardia, arterial hypotension, conductivity disorders, reduce the impact volume of the heart, which, apparently, is due to additive cardiodepressive and vasodilating effects.

With simultaneous use of tricyclic antidepressants, phenothiazines, asthymizol, terphelanadines cause an increase in the Qt interval and raising the risk of developing ventricular arrhythmias, especially the type "Pirouette".

With the simultaneous use of warfarin, phenprocaon, the anticoagulant action is enhanced and the risk of developing bleeding increases.

With the simultaneous use of vincamine, sutridge, erythromycin (intravenous), pentamidine (intravenously, intramuscularly) increases the risk of the development of ventricular arrhythmia of the type "PIRUET".

With simultaneous use, an increase in the concentration of dextromethorophane in the blood plasma is possible due to a decrease in the speed of its metabolism in the liver, which is due to the inhibition of the activity of the CYP2D6 of the cytochrome of the P450 system under the influence of amiodarone and the dextromethorophane dextrometerfranch slowdown.

With the simultaneous use of digoxin, the concentration of digoxin in the blood plasma is significantly increased by reducing its clearance and, as a result, the risk of developing digitalistic intoxication increases.

With the simultaneous use of diltiazem, the verapamil is increasing negative inotropic effect, bradycardia, conduction disorder, AV blockade.

A case of an increase in the concentration of amiodarone in the blood plasma with its simultaneous use with Indinavir is described. It is believed that Ritonavir, Nelfinavir, Savicinavir will have such an action.

With the simultaneous use of the cellular, the concentration of amiodarone in the blood plasma decreases due to its binding to the skewer and reduce absorption from the gastrointestinal tract.

There are reports of increasing the concentration of lidocaine in the blood plasma while using the amiodarone and the development of convulsion, apparently due to the inhibiting of the metabolism of lidocaine under the influence of amiodarone.

It is undesirable to combine amiodarone with alcohol and ethanol-containing products.

It is believed that synergism is possible with respect to the depressing action on the sinus node.

With the simultaneous use of lithium carbonate, hypothyroidism is possible.

With the simultaneous use of procanamide, the Qt interval is increasing due to an additive action on its magnitude and the risk of the development of ventricular tachycardia like "Pirouette". Increased concentration in the blood plasma of procanamide and its metabolite N-acetylpropairamide and enhancing side effects.

With the simultaneous use of propranolol, metoprolol, sotalol is possible arterial hypotension, bradycardia, ventricular fibrillation, asistolia.

With the simultaneous use of trazodon, the case of development of type "Pirouette" is described.

With the simultaneous use of quinidine, the Qt interval is increasing due to an additive action on its magnitude and the risk of developing ventricular tachycardia like "Pirouette". An increase in the concentration of quinidine in the blood plasma and the strengthening of its side effects.

With simultaneous use, a case of enhancing the side effects of clonazepam is described, which, apparently, is due to its cumulation due to the inhibition of oxidative metabolism in the liver under the influence of amiodarone.

With the simultaneous use of cisaprice, the Qt interval is significantly increasing due to an additive action, the risk of stomaching arrhythmias (including type "Pirouette").

With simultaneous use, the concentration of cyclosporine in the blood plasma increases, the risk of nephrotoxicity.

The case of pulmonary toxicity is described while simultaneously use of cyclophosphamide in high doses and amiodarone.

The concentration of amiodarone in the blood plasma increases due to the slowdown of its metabolism under the influence of cimetidine and other inhibitors of the microsomal liver enzymes.

It is believed that due to inhibition under the influence of the amodarone of liver enzymes, with the participation of which the metabolism of phenyotine occurs, it is possible to increase the concentration of the latter in the blood plasma and the strengthening of its side effects.

Due to the induction of microsomal liver enzymes under the influence of phenyodin, the rate of metabolism of amiodarone in the liver increases and its concentration is reduced in the blood plasma.

Analogs of the Medicinal Amyodar