KORDARON

Active material: Amiodarone
When ATH: C01BD01
CCF: Antiarrhythmic drugs
ICD-10 codes (testimony): I45.6, I47.1, I47.2, i48, I49.0, I49.4
When CSF: 01.11.01.03
Manufacturer: SANOFI-AVENTIS France (France)

Pharmaceutical form, composition and packaging

Pills from white to white with Valium a color shade, round, with a break line on one side, slant from the edges to the fault line and bevelled on both sides, engraved with a heart symbol on a fault line and figures “200” a fault line.

Excipients: lactose monohydrate, corn starch, magnesium stearate, polyvidone K90F, Colloidal anhydrous silica.

10 PC. – blisters (3) – packs cardboard.

The solution for the on / in the clear, light yellow.

Excipients: benzyl alcohol, polysorbate 80, water d / and.

3 ml – colorless glass vials (6) – packings Valium planimetric plastic (1) – packs cardboard.

Pharmacological action

Antiarrhythmic drugs. Amiodarone is a Class III (class of inhibitors of repolarization) and it has a unique mechanism of antiarrhythmic action, tk. in addition to the properties of Class III antiarrhythmics (Potassium channel blockade) it has the effect of Class I antiarrhythmic drugs (natrievыh blockade kanalov), Class IV antiarrhythmic drugs (calcium channel blockade) and noncompetitive beta-adrenoceptor blocking action.

In addition to the antiarrhythmic action of the drug are at an antianginal, koronarorasshiryayushtiy, alpha- and beta-adrenergic blocking effects.

Antiarrhythmic effect of the drug due to an increase in the duration of 3 phase of the action potential of cardiomyocytes, mainly by blocking potassium ion current in the canals (Class III antiarrhythmic effect on the classification of Vaughan-Williams); a decrease in sinus automatism, leading to a decrease in heart rate; неконкурентной блокадой a- и b-адренорецепторов; slowing sinoatrial, atrial and AV-conduction, more pronounced tachycardia; no change of ventricular conduction; increases refractory periods and reduction in myocardial excitability of the atria and ventricles, and an increase in the refractory period of AV-nodes; slowing and increasing the duration of the refractory period of additional beams of AV-.

Besides, Amiodarone has the following properties: no negative inotropic effect when administered; with a / in the introduction of a decrease in myocardial contractility by beta-adrenoceptor blocking action; reduction in myocardial oxygen consumption by a moderate decline in systemic vascular resistance and heart rate; an increase in coronary blood flow due to a direct effect on the smooth muscles of coronary arteries; maintenance of cardiac output by reducing the pressure in the aorta and reduce systemic vascular resistance; impact on the exchange of thyroid hormones: inhibition of the transformation T₃ in T₄ (Blockade thyroxine-5-deyodinazы) and blocking the capture of these hormones cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium; at / in the introduction – recovery of cardiac function in cardiac arrest, caused by ventricular fibrillation, resistant to cardioversion.

After receiving the drug inside the therapeutic effect develops after an average week (several days to 2 weeks). After termination receiving amiodarone determined in blood plasma within 9 months. It should take into account the possibility of saving the pharmacodynamic action of amiodarone for 10-30 days after its cancellation.

The on / in the introduction cordarone^® its activity reaches through 15 minutes and disappears after about 4 hours after injection.

Pharmacokinetics

Absorption

After a single oral dose C_max plasma levels achieved after 3-7 no. However, the therapeutic effect usually develops within a week after the start of dosing (several days to 2 weeks). The bioavailability after oral administration in different patients varies from 30% to 80% (an average value of about 50%).

After the on / in the cordarone^® amiodarone concentration in the blood decreases rapidly due to its entering the tissue. In the absence of repeated injections of the gradual withdrawal of amiodarone. With the resumption of his / in the introduction or in the appointment of the drug inside amiodarone accumulates in the tissues.

Distribution

Plasma protein binding is 95% (62% – albumin, 33.5% – beta-lipoproteinami). Amiodarone has a big V_d. Amiodarone has a slow entering the tissue and high affinity thereto. During the first days of treatment, the drug accumulates almost all tissues, particularly in adipose tissue and the liver but her, light, spleen and cornea.

The equilibrium state is reached later on 1 up to several months, depending on the individual patient.

Pharmacokinetics of the drug is explained by the use of loading doses, which is aimed at achieving the required level of rapid tissue penetration, It is causing them to exhibit a therapeutic effect of amiodarone.

Metabolism

It is metabolized in the liver. The major metabolite – dezetilamiodaron – pharmacologically active and can enhance the antiarrhythmic effect of a basic compound. Amiodarone is an inhibitor of the hepatic microsomal isoenzymes oxidation: CYP2С9, CYP2D6, CYP3А4, CYP3A5, CYP3А7.

Deduction

Withdrawal of amiodarone begins in a few days. Write mainly through the intestine. Amiodarone is characterized by a duration T_1/2 with great individual variability, therefore the selection of doses, eg, increase or decrease the, should be considered, that there should be, at least, 1 month for the stabilization of the new plasma concentrations of amiodarone).

Amiodarone and its metabolites are not displayed by hemodialysis.

Excretion ingestion takes place in 2 phase: T_1/2 in the α-phase – 4-21 no, T_1/2 in the β-phase – 25-110 days. After prolonged ingestion average T_1/2 – 40 days. After discontinuation of amiodarone complete elimination from the body may last for several months.

Kaƶdaja doza Kordarona^® (200 mg) It contains 75 mg iodine. Part of the iodine released from the drug found in the urine and in the form of iodide (6 mg for 24 hours at a daily dose of amiodarone 200 mg). Most of the iodine, It remains part of the drug, excreted in the feces after passage through the liver, However, if long-term treatment of amiodarone, the concentration of iodine can reach 60-80% kontsentratsiy of amiodarone.

Pharmacokinetics of the drug is explained by the use of loading doses, which is aimed at achieving the required level of quick soaking fabrics, It is causing them to exhibit its therapeutic effect.

Pharmacokinetics in special clinical situations

Amiodarone slightly excreted by the kidneys, therefore in patients with renal failure does not require correction dose.

Testimony

Orally

Relapse prevention:

- Life-threatening ventricular arrhythmias and ventricular fibrillation (treatment should be started in hospital under careful cardiac monitoring);

- Nadzheludochkovыh paroksizmalynыh tahikardiy, incl. documented recurrent episodes of paroxysmal supraventricular tachycardia stable in patients with organic heart disease; documented recurrent episodes of paroxysmal supraventricular tachycardia stable patients without organic heart disease, when other classes of antiarrhythmic drugs are not effective or are contra-indications to their use; documented recurrent episodes of paroxysmal supraventricular tachycardia stable patients with WPW syndrome;

- Mercatelʹnoj arrhythmias (Atrial Fibrillation) and atrial flutter.

Prevention of sudden arrhythmic death in patients at high risk:

- Patients with recent myocardial infarction, having a 10 PVCs in 1 no, Clinical manifestations of chronic heart failure and reduced left ventricular ejection fraction (<40%).

Kordaron^® It can be used in the treatment of arrhythmias in patients with coronary artery disease and / or impaired left ventricular function.

For i / v administration

- Mild asthma ventricular paroxysmal tachycardia;

- Mild asthma supraventricular paroxysmal tachycardia with high ventricular rate (especially against the WPW syndrome);

- Relief of paroxysmal and sustained atrial fibrillation (Atrial Fibrillation) and atrial flutter;

- Coronary cardiac arrest, caused by ventricular fibrillation, resistant to cardioversion.

Dosage regimen

Orally

In appointing the drug loading dose It can be used various schemes.

When used in a hospital initial dose, divided into several times, It is between 600-800 mg / day to a maximum 1200 mg / day to a total dose of 10 g (typically for 5-8 days).

At the outpatient use of the initial dose, divided into several times, It is between 600 mg 800 mg / day to a total dose of 10 g (typically for 10-14 days).

Maintenance dose can vary in different patients from 100 mg / day to 400 mg / day. It should use the minimum effective dose according to the individual therapeutic effects.

Unnecessarily. Amiodarone has a very long half-life, drug can be taken in a day or take a break in his reception 2 days per week.

Average therapeutic single dose – 200 mg. Average therapeutic daily dose – 400 mg.

The maximum single dose – 400 mg. The maximum daily dose – 1200 mg.

For i / v administration

Kordaron^® for / in the introduction is intended for use in cases, when a rapid achievement of antiarrhythmic effect, or if you can not use the drug inside.

Except for urgent clinical situations the drug should only be used in hospital intensive care unit under continuous ECG monitoring and blood pressure.

The on / in the introduction Kordaron^® It should not be mixed with other drugs or other medications administered simultaneously through the same venous access. The drug should be administered only in a diluted form. Üçün razvedenija Kordarona^® should only be used 5% Dextrose (Glucose). Due to the nature of the dosage form of the drug is not recommended to use a concentration of the infusion solution, less obtained by dilution 2 ampoules 500 ml 5% dextrose (Glucose).

In order to avoid reactions at the injection site Kordaron^® should be administered through a central venous catheter, except as coronary ventricular fibrillation, resistant to cardioversion, when in the absence of central venous access may be administered in a peripheral vein (Vienna is the largest peripheral blood flow with a maximum).

Severe cardiac arrhythmia, in cases, when it can not be received into nrenarata (except as coronary cardiac arrest, caused by ventricular fibrillation, resistant to cardioversion)

The drug is introduced into / in the drip through a central venous catheter.

Loading dose is, usually, 5 mg / kg body weight 250 ml 5% dextrose (Glucose), the administration is for 20-120 m, possibly, using electronic pumps. This dose can be re-entered 2-3 times during 24 no. Injection speed is adjusted depending on the clinical effect. Therapeutic effect appears during the first minutes of the introduction and gradually decreases after cessation of infusion, Therefore, if you need to continue the treatment injection form Kordarona^® It is recommended to switch to permanent/in drip infusion.

Maintenance doses: 10-20 mg/kg/24 h (usually 600-800 mg, but can be increased up to 1200 mg for 24 no) in 250 ml 5% dextrose (Glucose) within a few days. From the first day of infusion should begin a gradual transition to accept Kordarona^® oral dose 600 mg (3 tab.) per day. The dose may be increased to 800-1000 mg (4-5 tab.) per day.

Cardiology department with cardiac arrest, caused by ventricular fibrillation, resistant to cardioversion

The drug is introduced into / jet. The first dose of 300 mg (or 5 mg / kg) in 20 ml 5% dextrose (Glucose). If the fibrillation is not docked, Perhaps additional introduction of Kordarona^® in/in struino dose 150 mg (or 2.5 mg / kg).

Side effect

Determination of the frequency of adverse reactions: Often (≥ 10%), often (≥ 1%, <10); sometimes (≥ 0.1%, < 1%); rarely (≥ 0.01%, < 0.1%), rarely, including isolated reports (< 0/01%), Frequency unknown (According to reports the frequency cannot be determined).

If ingestion

Cardio-vascular system: often-moderate dozozawisimaya aetiology; sometimes – asequence (sinoatrialynaya blockade, AV-blokada different degrees), – aritmogennoe action (There are reports on the occurrence of new arrhythmias or exacerbating existing, in some cases – with the subsequent stopping of the heart; These effects are observed primarily in cases of Kordarona^® together with drugs, prolonging the QT interval_c or violations elektrolitnogo balance; in the light of the available data, it is impossible to determine, whether the occurrence of these arrhythmias Kordaronom^®, or due to the severity of cardiac pathology, or is a consequence of treatment failure); rarely – expressed aetiology or, in exceptional cases, Stop sinus (mainly in patients with sinus node dysfunction and elderly patients); unknown – progression of heart failure (prolonged use).

From the digestive system: Often – nausea, vomiting, decreased appetite, fatigue or loss of taste sensation, a feeling of heaviness in the epigastric (occur mostly at the beginning of treatment, pass after dose reduction), an isolated increase in transaminaz in the serum, usually moderate (excess of normal values in the 1.5-3 times; dropping at the same time reducing the dose or spontaneously); often – acute liver damage with increasing transaminaz and/or jaundice, including the development of liver failure, sometimes with fatal consequences; rarely – xronicheskie liver disease (psevdoalkogol'nyj hepatitis, cirrhosis) sometimes fatal. Even with a moderate increase in transaminaz in blood, observed after treatment, lasted more than 6 months, should be suspected chronic liver failure.

The respiratory system: often – Interstitial or alveolar Pneumonitis and bronchiolitis obliterans with pneumonia (sometimes with fatal consequences), pleurisy. These changes can lead to the development of pulmonary fibrosis, However, they mainly, reversible for early lifting of amiodarone with the appointment of corticosteroid or without appointment. Clinical manifestations usually disappear within 3-4 weeks. Restoration of the x-ray pictures and lung function occurs more slowly (several months). The appearance of the patient, receiving amiodarone, pronounced shortness of breath or dry cough, as involving, and not accompanied by a deterioration of the general condition of the (fatigue, weight loss, fever) requires a chest x-ray and, if necessary, drug withdrawal. Rarely – bronchospasm (in patients with severe respiratory failure, especially in patients with bronchial asthma), acute respiratory distress syndrome (sometimes fatal and sometimes directly after surgery; It is expected to interact with high doses of oxygen). Unknown – pneumorrhagia.

From the senses: Often – mikrootlozhenija in corneal epithelium, consisting of complex lipids, including lipofuscin, they are usually restricted to a region of the pupil and do not require stopping treatment and disappear after the drug, Sometimes they can cause impairment in the form of colored halos or fuzziness paths in bright light; rarely – optic neuritis/optic neuropathy (relationship with amiodarone to date not set; However, because optic neuritis may cause blindness, When you see the fuzziness of vision or reduced Visual acuity in the face of the reception Kordarona^® It is recommended that you conduct a complete ophthalmologic examination, including fundoskopiju, and in the case of optic neuritis stop receiving medication).

On the part of the endocrine system: often – gipotireoz (weight gain, chills may also appear, apathy, reduced activity, drowsiness, excessive compared to the expected effect of amiodarone bradycardia). Diagnosis is confirmed by detection of elevated serum TSH; normalization of thyroid gland is usually observed during 1-3 months after the end of treatment; in situations, associated with risk for life, amiodarone treatment may be continued, While the additional designation L-thyroxine under the supervision of TSH in serum). Also frequently occurs with hyperthyroidism, the appearance of which is possible during treatment and beyond (cases were reported of hyperthyroidism, developed a few months after the cancellation of amiodarone). Hyperthyroidism is more secretive with little symptoms: little unexplained weight loss, reducing the scale and/or efficiency of antianginal; psychiatric disorders in elderly patients, or even the phenomenon of thyrotoxicosis. Diagnosis is confirmed by detection of reduced serum TSH level (supersensitive criterion). When identifying hyperthyroidism amiodarone should be abolished. Normalization of thyroid gland usually occurs within several months after drug withdrawal. While the clinical semeiotics is normalised before (through 3-4 of the week), normalization occurs, the level of thyroid hormones. Severe cases can lead to fatal, in such cases, therefore, requires urgent medical intervention. Treatment in each case individually. If the patient's condition is deteriorating because of the thyrotoxicosis, and in connection with a dangerous imbalance between the need heart of oxygen and its delivery, It is recommended that you immediately begin treatment with corticosteroids (1 mg / kg), continuing his long enough (3 of the month), instead of applying synthetic anti tireoidnykh drugs, that may not always be effective in this case. Rarely – violations of ADH secretion syndrome.

Dermatological reactions: Often – photosensitivity; often (in the event of prolonged use of the drug in high daily doses) – grayish or bluish skin pigmentation (After the end of treatment this pigmentation is slowly disappearing); rarely – эritema (during radiation therapy), skin rash (usually malospecifichnaja), alopecia; in some cases – exfoliative dermatitis (connection with the admission of the drug is not installed).

CNS: often – tremor or other extrapyramidal symptoms, sleep disorders, nightmares; rarely – sensory-motor, motor and mixed peripheral neuropathy and/or myopathy (usually reversible after the drug); rarely – Cerebellar ataxia, benign intracranial hypertension (pseudotumor of the brain), headache.

From the hematopoietic system: rarely – thrombocytopenia, gemoliticheskaya anemia, aplasticheskaya anemia.

Other: rarely – vasculitis, epididymitis, several cases of impotence (the relationship with the product is not installed).

The on / in the introduction

Cardio-vascular system: often-moderate bradycardia, mainly moderate and transient decrease ad (cases of arterial expressed hypotension or collapse was observed in overdose or too fast a drug). Rarely – aritmogennoe action (There are reports on the occurrence of new arrhythmias in t. no. polymorphic ventricular tachycardia type “pirouette”, or exacerbating existing, in some cases – with the subsequent stopping of the heart; These effects are observed primarily in cases of Kordarona^® together with drugs, prolonging the QT interval_c or violations elektrolitnogo balance; in the light of the available data, it is impossible to determine, whether the occurrence of these arrhythmias Kordaronom^®, or due to the severity of cardiac pathology, or is a consequence of treatment failure); expressed aetiology or, in exceptional cases, Stop sinus (mainly in patients with sinus node dysfunction and elderly patients), rush of blood to the face, progression of heart failure (Perhaps the on/in the inkjet introduction).

The respiratory system: rarely – cough, breathlessness, interstitial pneumonitis, bronchoconstriction and/or sleep apnea (in patients with severe respiratory failure, especially in patients with bronchial asthma), acute respiratory distress syndrome (sometimes fatal and sometimes directly after surgery; It is expected to interact with high doses of oxygen).

From the digestive system: Often – nausea; rarely – isolated liver transaminaz in the serum (usually moderate, excess of normal values in the 1.5-3 times, dropping at the same time reducing the dose or even spontaneously), acute liver failure (during 24 h after injection of amiodarone) with increasing transaminaz and/or jaundice, including the development of liver failure, sometimes with fatal consequences.

Dermatological reactions: rarely – feeling the heat, increased perspiration.

CNS: benign intracranial hypertension (pseudotumor of the brain), headache.

Allergic reactions: rarely – anaphylactic shock; unknown – angioedema.

Local reactions: often – superficial phlebitis (When injected directly into a peripheral vein), pain, эritema, edema, necrosis, transsudacija, the infiltration, inflammation, packing, tromboflebit, phlebitis, cellulitis, infection, pigmentation.

Contraindications

- SSS (sinusovaya bradycardia, sinoatrialynaya blockade) except in the case of correction of artificial driver rhythm (danger “stop” sinus node);

-AV blockade II and III extent in the absence of a permanent artificial pacemaker (kardiostimuljatora);

— two- and trehpuchkovye blockade in the absence of a pacemaker; in these cases, the application Kordarona^® in/in is possible only in specialized offices under the guise of temporary pacemaker;

- Hypokalemia, gipomagniemiya;

- Severe hypotension, collapse, cardiogenic shock (for / in the);

is interstitial lung disease (orally);

-thyroid dysfunction (gipotireoz, hyperthyroidism);

— innate or acquired elongation QT interval;

-combination with drugs, capable of extending QT interval and cause development of paroxysmal tahikardij, including the polymorphous ventricular tachycardia type “pirouette”: Class IA antiarrhythmics (quinidine, gidroxinidin, disopyramide, prokaynamyd); class III antiarrhythmics (dofetilid, iʙutilid, bretiliya tosylate); sotalol; other (No antiarrhythmic) preparations, such as bepridil; vynkamyn; some neiroleptiki phenothiazines (chlorpromazine, ciamemazin, levomepromazin, tioridazin, trifluoperazine, fluphenazine), benzamidy (amisulpride, sultopryd, sul'prid, tiapride, veraliprid), butyrofenonы (droperidol, haloperidol), sertindole, pimozid; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular, erythromycin with on/in the introduction, spiramycine); azole; antimalarials (quinones, chloroquine, mefloxin, galofantrin); pentamidine in injecting introduction; difemanila metilsul'fat; mizolastin; astemizol, terfenadine; ftorkhinolony;

- Childhood and adolescence up 18 years (efficacy and safety have not been established);

- Pregnancy;

- Lactation;

-hypersensitivity to iodine and/or amiodaronu.

All the above listed contraindications do not refer to the application Kordarona^® When conducting kardioreanimacii with cardiac arrest, caused by atrial ventricular, resistant to cardioversion.

FROM caution should be applied inside and/in Decompensated or severe chronic (Functional class III-IV according to the classification of NYNA) Heart Failure, hepatic insufficiency, asthma, severe respiratory failure, in elderly patients (high risk of bradycardia), the AV-blockade 1 degrees; I / – When arterial hypotension.

Pregnancy and lactation

Kordaron^® is contraindicated in pregnancy and lactation (breast-feeding).

Currently available clinical information is insufficient to determine the degree of risk of malformations in the embryo when applying Kordarona^® I trimester of pregnancy.

Since the thyroid gland of the fetus begins to bind iodine only with 14 week of pregnancy (amenorrhea), It is not expected to impact on her evidence in case of an earlier application. Excess iodine in the application of the drug after this period may lead to lab symptoms of hypothyroidism in the newborn, or even to the formation he clinically significant goiter. In view of the impact of the drug on the fetal thyroid Cardarone^® contraindicated during pregnancy, except for the special cases of living testimony (When life ventricular violations heart rhythm).

Amiodarone is excreted into breast milk in significant amounts, therefore, if necessary, use during lactation should decide the issue of termination of breastfeeding.

Cautions

If ingestion

Side effects of amiodarone are doses, Therefore, to minimize the possibility of their occurrence, the drug should be used in the minimum effective dose.

Patients during treatment should avoid exposure to direct sunlight or to take protective measures (eg, use sunscreen, wearing appropriate clothing).

Before you start receiving amiodarone are advised to undertake a study of ECG and determining the level of potassium in the blood. Hypokalemia should be adjusted prior to the use of amiodarone. During treatment requires regular monitoring of ECG (every 3 of the month), the level transaminaz liver and other indicators of liver function.

Besides, because, that amiodarone could cause hypothyroidism or hyperthyroidism, especially in patients with thyroid disorder, before taking amiodarone should conduct clinical and laboratory (TSH content) survey to identify violations of the function and diseases of the thyroid gland. During treatment with amiodarone and within a few months after its termination requires regular surveys to identify clinical or laboratory signs of changes in thyroid function. In case of violation of the thyroid gland must spend identifying the level of TSH in serum.

Regardless of the presence or absence of amiodarone treatment during pulmonary symptoms are recommended every 6 months to carry out x-ray examination of the lungs and pulmonary functional tests.

Patients, long-term receiving treatment for arrhythmias, cases have been reported to increase the frequency of ventricular fibrillation and/or increase the threshold a pacemaker or implanted defibrillator, that may reduce their effectiveness. Therefore, before or during treatment Kordaronom^® You should regularly check the correct operation of these devices.

The emergence of breathlessness or dry cough as isolated, and accompanied by a deterioration of the general condition of the, indicates a possible pulmonary toxicity, such as interstitial pneumopathy, suspicion which requires an x-ray examination of the lungs and pulmonary functional tests.

As a result of lengthening the period of Ventricular Repolarization of the heart, the pharmacological action of Kordarona^® causes certain changes in the ECG: QT prolongation, QT_from (korrigirovannogo), may cause waves of U. It is permissible to increase the QT interval_c no more 450 Ms or not more than 25% from initial values. These changes are not a manifestation of the toxicity of the drug, However, require monitoring for dose adjustment and evaluation of possible proaritmogennogo actions Kordarona^®.

With the development of AV blockade II and III extent, sinoatrial blockade or dvuhpuchkovoj vnutrijeludockova blockade, treatment should be discontinued. When an AV blockade degree I requires strengthening clinical supervision.

While it was noted the occurrence of arrhythmias or exacerbation of existing disturbances, proaritmogenny effect of amiodarone is weak, less, than most complications drugs, and usually manifests itself in combination with certain drugs or violations elektrolitnogo balance.

When vague vision or when decreasing Visual acuity needed to conduct ophthalmologic examination, including the fundus examination. With the development of neuropathy or neuritis of the optic nerve, caused by amiodarone, the drug should be lifted because of the risk of blindness.

As Cardarone^® contains iodine, his technique can distort the results of radionuclide studies of the thyroid gland, However, it does not affect the accuracy of determination of the content of Tk, T4 and TSH in plasma.

Before surgery, you should notify a doctor anesthesiologist about how, that the patient receives Cardarone^®. Prolonged treatment Kordaronom^® may increase the risk of hemodynamic, proper local or general anesthesia. This applies especially to his bradikarditicheskim and hypotensive effects, reduced cardiac output and violations conductivity.

Besides, patients, receiving Cardarone^®, in rare cases, directly after surgery noted acute respiratory distress syndrome. During IVL such patients requires careful monitoring.

Effects on ability to drive vehicles and management mechanisms

During treatment Kordaronom^® should refrain from driving a car and activities potentially hazardous activities, require high concentration and speed of psychomotor reactions

The on / in the introduction

Except in urgent cases, in/in a Kordarona^® should be carried out only in the block of intensive therapy for continuous monitoring of ECG (with regard to the possibility of the development of bradycardia and aritmogennogo actions) and HELL.

Kordaron^® should be entered only in the form of infusions, tk. even very slow in/in a Jet can cause excessive decline ad, heart failure or severe respiratory failure.

For, to avoid reactions at the injection solution for the on/in the introduction, it is recommended that you enter through a central venous catheter. Only in the case of kardioreanimacii in cardiac arrest, caused by atrial ventricular, resistant to cardioversion, in the absence of central venous access (the lack of an established central venous catheter) the drug can be injected into a large peripheral vein with maximum blood flow.

If after kardioreanimacii treatment Kordaronom^® must go, What is Cardarone^® should be entered in/in drip through a central venous catheter under constant supervision of ad and ECG.

Kordaron^® It is not possible to confuse one sprite or Snyder with other drugs.

With regard to the possibility of interstitial pnevmonita when prompted after the introduction of the Kordarona^® pronounced shortness of breath or dry cough, as involving, and not accompanied by a deterioration of the general condition of the (fatigue, temperature increase) chest x-ray is required and, if necessary, cancel product, as the interstitial Pneumonitis may lead to the development of pulmonary fibrosis. However, these phenomena are basically, reversible for early lifting of amiodarone with the appointment of corticosteroid or without appointment. Clinical manifestations usually disappear within 3-4 weeks. Restoration of the x-ray pictures and lung function occurs more slowly (several months).

After The IVL (eg, When casting surgery) patients, which received Cardarone^® I /, There have been rare cases of acute respiratory distress syndrome, sometimes with fatal consequences (It is expected to interact with high doses of oxygen). Therefore, we recommend that you closely monitor the condition of such patients.

During the first days after the beginning of injection mold Kordarona^® may develop severe acute liver failure with the development of liver failure, sometimes fatal. It is recommended that regular monitoring of liver function during treatment Kordaronom^®.

Before surgical intervention anesthesiologist should be informed that, that the patient receives Cardarone^®. Treatment Kordaronom^® may increase the risk of hemodynamic, proper local or general anesthesia. This applies especially to his bradikarditicheskomu and gipotenzivnomu effects, reduced cardiac output and violations conductivity.

Combination with beta-adrenoblokatorami, In addition to sotalola (protivopokazannaja combination) and jesmolola (mixture, requires special care when applying), Verapamil and diltiazem, can be considered only in the context of prevention of life threatening ventricular arrhythmias and restore cardiac activity when you stop cepdca, caused by atrial ventricular, resistant to cardioversion.

It is important to take into account violations elektrolitnogo Exchange, especially the presence of hypokalemia, both factors, predisposing to proaritmogennomu action. Gipokaliemia should be adjusted to the application Kordarona^®.

Before starting treatment Kordaronom^® It is recommended that registration of ECG, and the level of potassium in the blood serum and identification of possible thyroid hormone levels (T₃, T₄ and TSH).

Side effects of the drug are usually dependent on the dose; Therefore, you should exercise caution when determining the minimum effective dose, to avoid or minimize the occurrence of adverse effects.

Amiodarone may cause thyroid dysfunction, especially in patients with impaired function of the thyroid gland in your own or family history. Therefore, in the case of a transition to accept Kordarona^® inside during treatment and a few months after the end of treatment should conduct a careful clinical and laboratory monitoring. With suspected thyroid dysfunction should be determining the level of TSH in serum.

Children safety and efficacy evidence not examined. In sealed injection Kordarona^® contains benzyl alcohol. It was reported on the development of the newborn dramatic choking fatalities after intravenous solutions, containing benzyl alcohol.

Overdose

Symptoms: When administered in excessive doses can sinusova aetiology, cardiac arrest, ventricular tachycardia, paroxizmalnaya ventricular tachyarrhythmia type “pirouette”, circulatory disorders, abnormal liver function, decrease in blood pressure.

Treatment: symptomatic therapy – gastric lavage, appointment of activated carbon (if the drug has recently adopted), When bradycardia – Beta-adrenostimuljatory or installing the pacemaker, When the tachycardia type “pirouette” – in/in the introduction of salts of magnesium or cardiostimulyatsia). Amiodarone and its metabolites are not removed when the dialysis. No specific antidote.

Information about overdose in the on/in the introduction Kordarona^® no.

Drug Interactions

Contraindicated in combination

Contraindicated use Kordarona^® in combination therapy with drugs, that can cause a polymorphous ventricular tachycardia type “pirouette”, tk. When they are combined with amiodarone increases the risk of this complication and death:

-antiarrhythmics: IA class (quinidine, gidroxinidin, disopyramide, prokaynamyd), Class III (dofetilid, iʙutilid, bretiliya tosylate), sotalol;

-other (No antiarrhythmic) preparations, such as bepridil; vynkamyn; Some antipsychotics: fenotiazinы (chlorpromazine, ciamemazin, levomepromazin, tioridazin, trifluoperazine, fluphenazine), benzamidy (amisulpride, sultopryd, sul'prid, tiapride, veraliprid), butyrofenonы (droperidol, haloperidol), sertindole, pimozid; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin in the on/in the introduction, spiramycine); azole;
protivomjaljarijnye tools (quinones, chloroquine, mefloxin, galofantrin, lumefantrine); pentamidine in injecting introduction; difemanila metilsul'fat; mizolastin; astemizol; terfenadine; ftorkhinolony (in particular, moxifloxacin).

Not recommended combinations

-Beta-adrenoblokatorami, with blokatorami “slow” calcium channel blockers, delay VARIATION (verapamil, diltiazem), tk. There is a risk of development of automaticity (bradycardia) and conductivity;

with laxatives, stimulating peristalsis, which can cause hypokalemia, which increases the risk of developing ventricular tachycardia type “pirouette”. During treatment Kordaronom^® Laxatives should be used by other groups.

Combinations, the application of which requires careful

With drugs, able cause hypokaliemia:

-Diuretics, causing hypokalemia (in monotherapy or combination);

-amphotericin b (I /);

-CORTICOSTEROIDS for system application H02;

— tetrakozaktid.

Increased risk of ventricular arrhythmias, particularly ventricular tachycardia type “pirouette” (hypokalemia is a predisposing factor). You want to control the content of electrolytes in the blood, if necessary – correction of hypokalemia, continuous clinical monitoring and ECG-monitoring. In the case of ventricular tachycardia type “pirouette” Beta-blockers should not be applied (should start ventricular kardiostimuljaciju, Perhaps in/with the introduction of magnesium salts).

With prokainamidom

Amiodarone may increase the plasma concentration of procainamide and its metabolite N-acetyl procainamide, that may increase the risk of side effects procainamide.

With antikoagulyantami indirect action

Amiodarone increases the concentration of warfarin through inhibition of izofermenta CYP2S9. With a combination of warfarin with amiodarone may increase the effects of indirect anticoagulant, that increases the risk of bleeding. Frequently monitor prothrombin time (INR) and a correction dose anticoagulant like during treatment with amiodarone, and after its abolition.

With cardiac glycosides (drugs naperstanki)

You may experience one or more violations of automatism (vыrazhennaya bradycardia) and atrioventricular conduction ventricular. Besides, with a combination of Digoxin with amiodarone may increase the concentration of Digoxin in plasma (due to the decrease in its clearance). Therefore, the combination of Digoxin with amiodarone, you must determine the concentration of Digoxin in the blood and monitor potential clinical and ECG manifestations of digitalisna intoxication. May require lower doses of Digoxin.

With jesmololom

Possible violations of contractility, automaticity and conductivity (Suppression of compensatory reactions of the sympathetic nervous system). Requires clinical and ECG- control.

With phenytoin (and, by extrapolation, with fosfenitoinom)

Amiodarone may increase plasma concentrations fenitoina through inhibition of izofermenta CYP2S9, so when combined with amiodarone may develop fenitoina overdose fenitoina, that can lead to neurological symptoms; need clinical monitoring and, at the first sign of overdose, reducing the dose of fenitoina, It is desirable to define concentration fenitoina plasma.

With flekainidom

Amiodarone increases plasma concentration flekainida through inhibition of CYP2D6 izofermenta. Which required correction doses of flekainida.

With drugs, those using izofermenta CYP3A4

When combined amiodarone, the inhibitor CYP3A4 izofermenta, with these drugs may increase their plasma concentrations, that may increase their toxicity and/or enhance the pharmacodynamic effects and may require lower doses of these drugs:

– Cyclosporine: perhaps increasing the concentration of Cyclosporine in the blood plasma, associated with decreased drug metabolism in liver, that can increase nefrotoksicescoe effects of Cyclosporine. It is necessary to define the concentration of Cyclosporine in the blood, monitoring of the kidneys and the correct dosage of Cyclosporine during treatment and after withdrawal of the drug amiodarone.

– Fentanyl: in combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of its toxic effects.

– Other drugs, metabolizirujushhiesja with the participation of CYP3A4: lidokain (the risk of sinus bradycardia and neurological symptoms), tacrolimus (risk of Nephrotoxicity), sildenafil (the risk increase its side effects), midazolam (risk of psychomotor effects), triazolam, digidroergotamin, ergotamin, Statins, including simvastatin (increased risk of muscle toxicity, rhabdomyolysis, Hence the dose of simvastatin should not exceed 20 mg / day, when its inefficiency should go to accept another statina, metabolizirujushhegosja not using CYP3A4).

With orlistatom

There is a risk of reduced concentrations of amiodarone and its active metabolite in blood plasma. Required clinical and, if necessary, ECG-monitoring.

With clonidine, guanfacinom, cholinesterase inhibitors (donepezilom, galantaminom, rivastigminom, takrinom, ambenonija chloride, piridostigmina bromide, neostigmina bromide), pilokarpinom

There is a risk of excessive bradycardia (cumulative effects).

With cimetidine, grapefruit juice

There has been a slowing of the metabolism of amiodarone and increase its plasma concentrations, Perhaps an increase in the pharmacodynamic and adverse effects of amiodarone.

With drugs for inhalation narcosis

It has been reported that the development of the following severe complications in patients, receiving amiodarone, When performing anesthesia: ʙradikardii (resistant to the introduction of atropine), hypotension, conduction disturbances, decrease cardiac output. Experienced very rare cases of severe complications from the respiratory system (acute respiratory distress syndrome, adult), sometimes fatal, that evolved directly after surgery, which is associated with high concentrations of oxygen.

With radioactive iodine

Amiodarone contains iodine and, therefore, may interfere with the absorption of radioactive iodine, that can skew the results of radionuclide studies of the thyroid gland.

With rifampicin

Rifampin is a potent inducer of CYP3A4, Therefore, when coupled with the use of amiodarone may reduce plasma concentrations amiodarone and dezjetilamiodarona.

With St. John's wort preparations

St. John's wort is a potent inducer of SYR3A4. In this regard, it is theoretically possible to decrease plasma concentration of amiodarone and its effect (clinical data are not available).

HIV protease inhibitors (incl. indinavir)

HIV protease inhibitors are inhibitors of SYR3A4, Therefore, together with the use of amiodarone may increase the concentration of amiodarone in the blood.

With klopidogrelom

Clopidogrel, is the inactive drug tienopirimidinovym, It is metabolized in the liver with the formation of active metabolites. The interaction between klopidogrelom and amiodarone, that could result in diminishing the effectiveness of klopidogrela.

With dekstrometorfanom

Dextromethorphan is a substrate of CYP2D6 and CYP3A4. Amiodarone inhibits the CYP2D6 and could theoretically increase the plasma concentration of dextromethorphan.

Conditions of supply of pharmacies

The drug is released under the prescription. Preparation in the form of solution for the on/in the introduction is intended for use only in a hospital environment.

Conditions and terms

List B.

Preparation in the form of tablets should be stored at a temperature of no higher than 30° c. Shelf life – 3 year.

Preparation in the form of solution for the on/in the introduction should be stored at a temperature of no higher than 25° c. Shelf life – 2 year.

The drug should be stored out of reach of children.