Cordarone - instructions for use, doses, side effects, contraindications

Description:Round tablets from white to white with a creamy shade of color with a fault line on one side and with a facet on both sides. There is an engraving: a heart symbol above the fault line and 200 under the fault line and a bevel from the edges to the fault line.

Pharmacotherapeutic group:antiarrhythmic drug

ATX: & nbsp

C.01.B.D.01 Amiodarone

Pharmacodynamics:

Amiodarone belongs to the third class of antiarrhythmic drugs (repolarization inhibitor class) and has a unique mechanism of antiarrhythmic action, in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (blockade of sodium channels), class IV antiarrhythmics (calcium channel blockade ) and non-competitive beta-adrenergic blocking action.

In addition to antiarrhythmic action, he has antianginal, coronary dilatory, alpha and beta adrenoblocking effects.

Antiarrhythmic properties:

an increase in the duration of the third phase of the action potential of cardiomyocytes, mainly due to the blocking of the ion current in the potassium channels (anti-arrhythmic effect of class III according to Williams classification);

a decrease in the automatism of the sinus node, which leads to a decrease in the heart rate;

non-competitive blockade of alpha- and beta-adrenergic receptors; slowing of sinoatrial, atrial and atrioventricular conduction, more pronounced with tachycardia; no changes in ventricular conduction;

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

slowing the conduction and prolongation of the refractory period in additional beams of the atrioventricular conduction.

Other effects:

absence of negative inotropic effect when taken orally; decrease in oxygen consumption by myocardium due to a moderate decrease in peripheral resistance and heart rate; increase in coronary blood flow due to direct effect on the smooth muscles of the coronary arteries;

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

influence on the exchange of thyroid hormones: inhibition of the transformation of T3 into T4

(blockade of thyroxine-5-deiodinase) and blocking the seizure of these hormones by cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium.

Therapeutic effects are observed on average a week after the start of the drug (from several days to two weeks). After the termination of its reception amiodarone is determined in the blood plasma for 9 months. It should be taken into account the possibility of maintaining the pharmacodynamic action of amiodarone within 10-30 days after its withdrawal.

Pharmacokinetics:

Bioavailability after ingestion varies from 30 to 80% in different patients (mean value about 50%). After a single intake of amiodarone, the maximum plasma concentrations are reached after 3-7 hours. However, the therapeutic effect usually develops one week after the start of the drug (from several days to two weeks). Amiodarone is a drug with a slow intake of tissue and high affinity for them.

The connection with plasma proteins is 95% (62% with albumin, 33.5% with beta-lipoproteins). Amiodarone has a large volume of distribution.During the first days of treatment, the drug accumulates in almost all tissues, especially in adipose tissue and, in addition, in the liver, lungs, spleen and cornea.

Amiodarone is metabolized in the liver with the help of isozymes CYP3A4 and CYP2C8. Its main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the basic compound. Amiodarone and its active metabolite, desethylamiodarone in vitro, have the ability to inhibit isoenzymes CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and desethylamiodarone also demonstrated the ability to inhibit certain transporters, such as P-glycoprotein (P-gp) and an organic cation carrier (PKK2). In vivo, the interaction of amiodarone with the substrates of the isoenzymes CYP3A4, CYP2C9, CYP2D6 and P-gp was observed.

The removal of amiodarone begins in a few days, and the achievement of a balance between the admission and withdrawal of the drug (the achievement of the equilibrium state) occurs after one to several months, depending on the individual characteristics of the patient. The main way to remove amiodarone is the intestine. Amiodarone and its metabolites are not excreted by hemodialysis. Amiodarone has a long half-life with a large individual variability (therefore, when choosing a dose, for example, increasing or decreasing it, it should be remembered that at least 1 month is needed to stabilize a new plasma concentration amiodarone).

Excretion during ingestion proceeds in 2 phases: the initial half-life (the first phase) is 4-21 hours, the half-life in the second phase is 25-110 days. After continued oral administration, the average half-life is 40 days. After the withdrawal of 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 found in urine in the form of iodide (6 mg for 24 hours with a daily dose of amiodarone 200 mg). Most of the iodine remaining in the drug is excreted through the intestine after passing through the liver, however, with prolonged administration of amiodarone, the concentration of iodine in the blood can reach 60-80% of the concentrations of amiodarone in the blood. Features of the pharmacokinetics of the drug explains the use of "loading" doses, which is aimed at the rapid accumulation of amiodarone in tissues, in which its therapeutic effect is manifested.

Pharmacokinetics in renal failure: due to the insignificant kidney excretion in patients with renal insufficiency, dose adjustment of amiodarone is not required.

Indications:

Life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be initiated in a hospital with careful cardiac monitoring).

Supraclavicular paroxysmal tachycardias:

documented attacks of recurrent persistent supraventricular paroxysmal tachycardia in patients with organic heart disease;

documented attacks of recurrent persistent supraventricular paroxysmal tachycardia in patients without organic heart disease, when antiarrhythmic drugs of other classes are not effective or there are contraindications to their use;

documented attacks of recurrent persistent supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome.

Atrial fibrillation (atrial fibrillation) and atrial flutter Preventing sudden arrhythmic death in high-risk patients

- Patients after a recent myocardial infarction who have more than 10 ventricular extrasystoles per hour, clinical manifestations of chronic heart failure and a reduced fraction of left ventricular ejection (less than 40%).

Cordarone® can be used in the treatment of rhythm disturbances in patients with coronary heart disease and / or impaired left ventricular function.

Contraindications:

Hypersensitivity to iodine, amiodarone or excipients of the drug.

Intolerance to galactose, lactase deficiency, glucose-galactose malabsorption syndrome (the preparation contains lactose).

Syndrome of weakness of the sinus node, sinus bradycardia, sinoatrial blockade in the absence of the patient's installed artificial pacemaker (pacemaker) (risk of "stopping" the sinus node).

Atrioventricular blockade of II-III degree, in the absence of an established artificial pacemaker (pacemaker) in the patient.

Hypokalemia, hypomagnesemia.

Combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including ventricular "pirouette" tachycardia (see Fig.section "Interaction with other drugs"):

- antiarrhythmic drugs: IA class (quinidine, hydroquinidine, disopyramide procainamide); antiarrhythmic drugs III class (dofetilide, ibutilide, brethil tosylate); sotalol; other (non-antiarrhythmic) drugs, such as beprideal; wincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, verialpyride), b tyrofenoi (droperidol. haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine with parenteral administration; dipemanyl methyl sulfate; misolastine; astemizole, terfenadine; fluoroquinolones.

Congenital or acquired lengthening of the QT interval.

Thyroid dysfunction (hypothyroidism, hyperthyroidism).

Interstitial lung disease.

Pregnancy (except in special cases,section "Application during pregnancy and during lactation").

Lactation period (see section "Application during pregnancy and during lactation").

Age to 18 years (effectiveness and safety not established).

Carefully:

With decompensated or severe chronic (III-IV FC by classification NYHA) heart failure, hepatic insufficiency, bronchial asthma, severe respiratory failure, in elderly patients (high risk of severe bradycardia), with atrioventricular blockade of the I degree.

Pregnancy and lactation:

Currently available clinical information is not sufficient to determine whether embryos can develop or develop in the first trimester of pregnancy.

Since the fetal thyroid begins to bind iodine only from the 14th week of pregnancy (amenorrhea), then it is not expected that amiodarone will affect it if it is used earlier. Excess iodine in the use of the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in a newborn or even to the formation of a clinically significant goiter in it.

Due to the effect of the drug on the thyroid gland of the fetus, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit exceeds the risks (with life-threatening ventricular arrhythmias).

Breastfeeding period

Amiodarone is excreted in breast milk in significant quantities, so it is contraindicated during breastfeeding (so during this period the drug should be canceled or stopped breastfeeding).

Dosing and Administration:

The drug should be taken only as directed by a doctor!

Cordarone® tablets are taken orally before meals and are washed down with a sufficient amount of water.

Load ("saturating") dose: different saturation schemes can be applied.

In the hospital: the initial dose divided into several doses ranges from 600-800 mg (to a maximum of 1200 mg) per day until a total dose of 10 g is reached (usually within 5-8 days).

Ambulatory: the initial dose divided into several doses ranges from 600 to 800 mg per day until a total dose of 10 g (usually within 10-14 days).

Maintenance dose: can vary in different patients from 100 to 400 mg / day. A minimum effective dose should be applied in accordance with the individual therapeutic effect.

Since Cordarone® has a very long half-life, it can be taken every other day or take breaks in its reception 2 days a week.

The average therapeutic single dose 200 mg.

The average therapeutic daily dose 400 mg.

Maximum single dose - 400 mg.

The maximum daily dose - 1200 mg.

Side effects:

The incidence of adverse events was determined in accordance with the classification of the World Health Organization (WHO): very often (> 10%); often (> 1%, <10%); infrequently (> 0.1%, <1%); rarely (> 0.01%, <0.1%) and very rarely, including individual reports (<0.01%); the frequency is unknown (it is not possible to determine the frequency from the available data).

Violations from the blood and lymphatic system: Very rarely - Hemolytic anemia, aplastic anemia, thrombocytopenia. The frequency is unknown - neutropenia, agranulocytosis.

Heart Disease: Often - Bradycardia, usually mild and dose-dependent. Infrequent - Arrhythmogenic action (the occurrence of new rhythm disturbances or weighting of existing rhythm disturbances, in some cases with subsequent cardiac arrest) (see section "Interaction with other drugs and").Very rarely - Severe bradycardia or sinus node arrest in patients with sinus node dysfunction and / or elderly patients. Frequency unknown - Conductivity disorders (sinoatrial block, atrioventricular blockage of various degrees of severity). Ventricular "pirouette" tachycardia (see section "Interaction with other drugs", subsection "Pharmacodynamic interaction" and section "Special instructions").

Disorders from the endocrine system: Often - Hypothyroidism. Hyperthyroidism, sometimes fatal. Very rarely - Syndrome of impaired secretion of antidiuretic hormone.

Disorders from the side of the organ of vision: Very often - Microdeposition in the epithelium of the cornea, consisting of complex lipids. They are usually limited to the area of the pupil and disappear after the drug is discontinued. Sometimes they can cause visual disturbances in the form of a color halo in bright light or blurred vision. Very rarely - neuropathy / optic neuritis, which can progress to the development of blindness.

Disorders from the digestive system: Very often - Nausea, vomiting, dysgeusia (dullness or loss of taste sensations), usually occurring when taking a loading dose and passing after a dose reduction.The frequency is unknown - Pancreatitis / acute pancreatitis, dryness of the oral mucosa, constipation.

General disorders: Frequency unknown - Formation of granulomas, including bone marrow granuloma.

Disorders from the liver and bile ducts: Very often - Isolated increase in serum transaminase activity, usually mild (exceeding the upper limit of the norm from 1.5 to 3 times), observed at the beginning of treatment. The activity of "hepatic" transaminases can return to normal values with decreasing dose or even spontaneously. Often - Acute liver damage with increased transaminase activity and / or jaundice, including development of hepatic insufficiency, sometimes fatal (see section "Special instructions"). Very rarely - Chronic liver disease (pseudo-alcoholic hepatitis, cirrhosis), sometimes fatal.

Immune system disorders: Frequency unknown - Angioedema (Quincke's edema), anaphylactic / anaphylactoid reactions, including shock.

Laboratory and instrumental data: Very rarely - Increased serum creatinine concentration.

Disorders from the metabolism and nutrition: Frequency unknown - Decreased appetite.

Disturbances from the nervous system: Often - Extrapyramidal tremor, nightmarish dreams, sleep disturbances. Infrequent - Peripheral sensory-motor neuropathy and / or myopathy, usually reversible after drug withdrawal. Very rarely - Cerebellar ataxia, benign intracranial hypertension (pseudotumor of the brain), headache. The frequency is unknown - Parkinsonism, parosmia (odor disorder, especially subjective perception of odor, objectively absent).

Disorders of the psyche: Frequency unknown - Condition of confusion / delirium, hallucinations.

Violation of the genitals and mammary gland: Very rarely - Epididymitis, impotence. Frequency unknown - Decreased libido.

Disturbances from the respiratory system, chest and mediastinal organs: Often - Pulmonary toxicity (alveolar / and interstitial pneumonitis or fibrosis, pleurisy, obliterating bronchiolitis with arranging pneumonia [cryptogenic openerizing pneumonia]), sometimes fatal.Very rarely - Bronchospasm in patients with severe respiratory failure, especially in patients with bronchial asthma. Acute adult respiratory distress syndrome, sometimes fatal, usually developing immediately after surgery (possible interaction with high concentrations of oxygen) (see sections "Special instructions", "Interaction with other drugs"). Frequency unknown - Pulmonary bleeding.

Disturbances from the skin and subcutaneous tissues: Very often - Photosensitivity. Often - In case of prolonged use of the drug in high daily doses, grayish or bluish skin pigmentation may be observed; after the cessation of treatment, this pigmentation slowly disappears. Very rarely - There are cases of erythema during radiation therapy; skin rash, usually nonspecific, exfoliative dermatitis, alopecia. Frequency unknown - Eczema, urticaria, severe skin reactions, sometimes fatal, including toxic epidermal necrolysis / Stevens-Johnson syndrome, bullous dermis; drug reaction with eosinophilia and systemic symptoms.

Violations from the vessels: very rarely - vasculitis.

Overdose:

When ingesting very large doses, several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal ventricular "pirouette" tachycardia, and liver damage are described. It is possible to slow the atrioventricular conduction, to strengthen the already existing heart failure.

Treatment should be symptomatic (gastric lavage, use of activated charcoal (if the drug is taken recently), in the remaining cases, symptomatic therapy is performed: with bradycardia - beta-adrenostimulants or pacemaker installation, with ventricular "pirouette" tachycardia - iv administration of magnesium salts or pacing .

Neither amiodarone, nor its metabolites are removed during hemodialysis.

There is no specific antidote.

Interaction:

Pharmacodynamic interaction

Medicines that can cause a bidirectional ventricular "pirouette" tachycardia or increase the duration of the OT interval Drugs that can cause ventricular "pirouette" tachycardia

Combination therapy with drugs that can cause ventricular "pirouette" tachycardia is contraindicated, as this increases the risk of developing a potentially lethal ventricular "pirouette" tachycardia. These include: - antiarrhythmic drugs: IA class (quinidine, hydroquinidine. disopyramide, procainamide), sotalol, benridyl; - other (non-antiarrhythmic) medicines, such as wincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with intravenous administration, spiramycin); azoles; antimalarial medicines (quinine, chloroquine, mefloquine, halofantrip, lumefantrine); pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine; astemizole; terfenadine.

Drugs that can increase the duration of the QT interval

Joint administration of amiodarone with drugs that are able to increase the duration of the QT interval should be based on a careful assessment for each patient of the relationship between expected benefit and potential risk (the possibility of an increased risk of developing ventricular "pirouette" tachycardia) (see section "Special instructions"), such combinations it is necessary to constantly monitor the ECG of patients (to detect the prolongation of the QT interval), as well as the content of potassium and magnesium in the blood. In patients receiving amiodarone, fluoroquinolones should be avoided, including moxifloxacin.

Medicines that reduce heart rate, or cause violations of automatism or conduction

Combination therapy with these drugs is not recommended.

Beta-adrenoblockers, blockers of "slow" calcium channels, which cut heart rate (verapamil, diltiazem), can cause violations of automatism (the development of excessive bradycardia) and conduction.

Medicines that can cause hypokalemia

Not recommended combinations - With laxatives that stimulate intestinal peristalsis, which can cause hypokalemia. increasing the risk of developing ventricular "pirouette" tachycardia.Simultaneously with amiodarone, laxatives of other groups should be used.

Combinations, requiring caution when applying

With diuretics causing hypokalemia (in monotherapy or in combination with other drugs).

With systemic corticosteroids (glucocorticosteroids, mineralocorticosteroids), tetracosactide.

With amphoteric B (intravenous).

It is necessary to prevent the development of hypokalemia, and in case of its occurrence, to restore to normal values the potassium content in the blood, to control the electrolytes in the blood and the ECG (for possible prolongation of the QT interval). and in the case of ventricular "pirouette" tachycardia, antiarrhythmics should not be used (ventricular pacing should be started, intravenous magnesium salts may be introduced). Medicines for general anesthesia

The possibility of developing the following serious complications in patients taking amiodarone, with general anesthesia: bradycardia (resistant to atropine administration), reduction arterial pressure, conduction disorders, reduction of cardiac output.

There were very rare cases of serious complications from the respiratory system, sometimes fatal (acute adult respiratory distress syndrome) which developed immediately after surgery, the occurrence of which is associated with an interaction with high concentrations of oxygen.

Medicines that reduce heart rate (clonidine, guangfah. cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmia bromide), pilocarpine)

The risk of developing excessive bradycardia (cumulative effects).

Influence of amiodarone on other drugs

Amiodarone and / or its metabolite dezetilamiodaron inhibit isozymes CYP1AI, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-gp and may increase the systemic exposure of drugs which are their substrates. Due to the long half-life of amiodarone, this reaction can be observed even after a few months after stopping it.

Drugs that are substrates of P-gp

Amiodarone is an inhibitor of P-gp.It is expected that his joint intake with drugs and substrates P-gp, will lead to an increase in the systemic exposure of the latter.

Cardiac glycosides (digitalis preparations)

The possibility of violations of automatism (pronounced bradycardia) and atrial-ventricular conduction. In addition, with the combination of digoxin with amiodarone, an increase in the concentration of digoxin in the blood plasma is possible (due to a decrease in its clearance). Therefore, when digoxin is combined with amiodarone, it is necessary to determine the concentration of digoxin in the blood and to monitor possible clinical and electrocardiographic manifestations of digitalis intoxication. You may need to reduce the dosage of digoxin.

Dabigatran

Care should be taken when using amiodarone and dabigatran at the same time because of the risk of bleeding. Dabigatran dose may need to be adjusted in accordance with the instructions in its instructions for use.

Drugs that are substrates of the isoenzyme CYP2C9

Amiodarone increases the concentration in the blood of drugs that are substrates of the isoenzyme CYP2C9. such as warfare or phenytoin by inhibiting the isoenzyme CYP2C9.

Warfarin

When warfarin is combined with amiodarone, the effects of an indirect anticoagulant may increase, which increases the risk of bleeding. It should be more often monitor prothrombin time by determining the INR (international normalized ratio) and correcting the doses of indirect anticoagulants, either during treatment with amiodarone or after stopping it.

Phenytoin

When phenytoin is combined with amiodarone, an overdose of phenytoin may develop, which may lead to the appearance of neurologic symptoms; it is necessary to monitor clinically and reduce the dose of phenytoin at the first signs of an overdose, it is desirable to determine the concentration of phenytoin in the blood plasma.

Drugs that are substrates of the isoenzyme CYP2D6

Flecainide

Amiodarone raises the plasma concentration of flecainide by inhibiting the isoenzyme CYP2D6, which requires the correction of doses of flecainide.

Drugs that are substrates of the isoenzyme CYP3A4 When combined with amiodarone, an isofermene inhibitor CYP3A4,these drugs can increase their plasma concentrations, which can lead to an increase in their toxicity and / or increased pharmacodynamic effects, and may require a reduction in their doses. Such medicines are listed below.

Cyclosporin

The combination of cyclosporine with amiodarone may increase the concentration of cyclosporine in the blood plasma, a dose adjustment is necessary.

Fentanyl

The combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects.

Inhibitors of HMG-CoA reductase (statins) (simvastatin, atorvastatin and lovastatii)

Increased risk of muscle toxicity (rhabdomyolysis) with simultaneous use of amiodarone and statins. metabolized by the isoenzyme CYP3A4. It is recommended to use statins that are not metabolized by the CYP3A4 isoenzyme.

Other drugs metabolized by the isoenzyme CYP3A4: lidocaine (risk of developing sinus bradycardia and neurologic symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (the risk of increasing its side effects), midazolam (risk of development of psychomotor effects), triazolam. dihydroergotamine. ergotamine. colchicine.

A drug that is a substrate of the isoenzymes CYP2D6 and CYP3A4.

Dextromethorphan

Amiodarone inhibits the isoenzymes CYP2D6 and CYP3A4 and can theoretically increase the plasma concentration of dextromethorphan.

Clopidogrel

Clopidogrel, which is an inactive thienopyrimidine drug metabolized in the liver with the formation of active metabolites. Possible interaction between clopidogrel and amiodarone, which can lead to a decrease in the effectiveness of clopidogrel.

The effect of other drugs on amiodarone

Inhibitors of CYP3A4 and CYP2C8 isoenzymes may have the potential to inhibit the metabolism of amiodarone, increase its concentration in the blood and, accordingly, the risk of increasing its pharmacodynamic and side effects.

It is recommended to avoid taking inhibitors of the isoenzyme CYP3A4 (for example, grapefruit juice and certain medicines such as cimetidine and HIV protease inhibitors (including, indinavir) during treatment with amiodarone. Inhibitors of HIV protease, when used simultaneously with amiodarone, can increase the concentration of amiodarone in the blood. Inductors of the isoenzyme CYP3A4

Rifampicin

Rifampicin is a potent inducer of isoenzyme CYP3A4, when combined with amiodarone it can reduce the plasma concentration of amiodarone and dezetilamiodarona.

Preparations of St. John's Wort

St. John's wort is a potent inducer of CYP3A4 isoenzyme. In this regard, it is theoretically possible to reduce the plasma concentration of amiodarone and reduce its effect (no clinical data are available).

Special instructions:

Kordaron® side effects of the drug are usually dose-dependent, so to minimize the possibility of their occurrence should apply the minimum effective dose. Patients should be warned that during treatment they avoid exposure to direct sunlight or take protective measures (for example, the use of sunscreen, wearing appropriate clothing). Response from the heart Kordaron® pharmacological action of the drug causes ECG changes: lengthening the interval QT, QTc (korregirovat) associated with the extension of the period of ventricular repolarization of the heart, with the possible appearance of waves U. However, these changes are not a manifestation of the toxic effect Kordaron® preparation.It is permissible to increase the Q-Tc interval by more than 450 ms or not more than 25% of the initial value.

In elderly patients, a significant slowdown in heart rate is possible. With the development of atrioventricular blockade II and grade III, sinoatrial blockade or a two-beam intraventricular blockade, treatment with Cordarone® should be discontinued. When an atrioventricular block of degree I occurs, the observation should be strengthened.

There were reports of new rhythm disturbances or weighting of already existing rhythm disturbances, sometimes with a legal outcome. It is very important, but it is difficult to make a differential diagnosis between insufficient effectiveness of the drug and its arrhythmogenic effect, whether combined or not with aggravation of the severity of the cardiovascular pathology. The use of Cordarone® for arrhythmogenic action was reported significantly less frequently than with other antiarrhythmic drugs and was generally observed in the presence of factors that increased the duration of the QT interval, such as interaction with other drugs and / or impaired electrolyte content in the blood (cm.sections "Side effect" and "Interaction with other drugs"). Despite the ability of Cordarone® to increase the duration of the QT interval, it showed low activity with respect to provoking ventricular "pirouette" tachycardia.

Hyperthyroidism (see section "Side effect"). During the administration of Cordarone®, or for several months after its discontinuation, hyperthyroidism may develop. Clinical manifestations are usually mild, so symptoms such as weight loss, the occurrence of rhythm disorders, angina attacks, the development of chronic heart failure should alert the doctor. The diagnosis is confirmed by the detection of a decrease in the serum TSH concentration, determined with the help of an ultrasensitive test on TSH. In this case, the drug Cordarone® should be discontinued. Recovery usually occurs within a few months after the withdrawal of treatment: first there is a disappearance of clinical manifestations, and then normalization of laboratory parameters of thyroid function takes place.Severe cases of thyrotoxicosis, which can sometimes lead to death (both due to thyrotoxicosis itself and due to a dangerous imbalance between myocardial oxygen demand and delivery) require urgent treatment. Treatment should be selected in each case individually: antithyroid drugs (which may not always be affective), glucocorticosteroids, beta-adrenergic blockers.

Neuromuscular disorders (see section "Adverse Effects")

A drug Cordarone® can cause peripheral sensory-motor neuropathy and / or myopathy. Recovery usually occurs within a few months after the withdrawal of Cordarone®, but may sometimes be incomplete.

Disturbances on the part of the organ of sight

With a vague vision or with reduced visual acuity, a complete ophthalmological examination, including examination of the fundus (fundoscopy), should be performed urgently. When neuropathy and / or optic neuritis are detected, Cordarone® must be discontinued because of the danger of their progression to the development of blindness.

Pulmonary disorders

The appearance of dyspnea or dry cough may be associated with pulmonary toxicity, in particular with the development of interstitial pneumonitis. If suspected development of interstitial pneumonitis in patients who have severe dyspnoea, both isolated and in combination with worsening of the general condition (fatigue, weight loss, fever), an X-ray examination of the lungs should be performed. A reassessment of the use of Cordarone® should be reassessed, because with its early cancellation, interstitial pneumonitis is usually reversible (clinical symptoms are usually resolved within 3-4 weeks, followed by a slower improvement in the radiographic pattern and lung function 15 for several months). Consideration should be given to the treatment of glucocorticosteroids.

In addition, in patients who took Cordarone®, in very rare cases, usually immediately after surgery, a serious respiratory complication (acute respiratory distress syndrome of adults), sometimes fatal, was observed; it is possible to link its development with interaction with high concentrations of oxygen (see section "Side effect").

Disorders from the side of the liver

It is recommended that the functional "liver" tests (monitoring the activity of "liver" transaminases) be carefully monitored before starting the Cordarone® preparation and regularly during the treatment with the drug. When taking Cordarone ®, acute abnormalities of function are possible liver (including hepatocellular insufficiency or liver failure, sometimes with a fatal outcome) and chronic liver damage. Therefore, when the activity of "hepatic" transaminases increases, which is 3 times higher than the upper limit of the norm, the dose of Cordarone® should be reduced or stopped. Clinical and laboratory signs of chronic liver failure with Cordarone® oral administration can be minimally expressed (hepatomegaly, an increase in the activity of transaminases 5 times higher than the upper limit of the norm) and reversible after discontinuation of the drug, however, deaths have been reported.

Severe bullous reactions

Kordarone® should be discontinued immediately if symptoms and manifestations of life-threatening or even fatal reactions occur in the form of Stephen-Johnson syndrome, toxic epidermal necrolysis,namely: the appearance of progressive skin rash, often with the formation of blisters, or damage to the mucous membranes.

Drug Interactions

It is not recommended simultaneous use of the drug Cordarone® with the following drugs: beta-adrenoblockers, blockers of "slow" calcium channels, which cut heart rate (verapamil, diltiazem); Laxative stimulating the peristalsis of the intestine, which can cause hypokalemia.

Monitoring of treatment

Before starting the Cordarone® treatment, it is recommended that an ECG and a serum potassium test be performed. Hypokalemia should be corrected before starting Cordarone®. During treatment, it is necessary to regularly monitor the ECG, as well as the activity of "liver" transaminases and other indicators of liver function.

In addition, because Kordarone® can cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, a clinical and laboratory examination should be performed prior to taking Cordarone® for thyroid dysfunction(concentration of serum TSH, determined with the help of ultrasensitive analysis on TSH). During treatment with Cordarone® and several months after discontinuation, the patient should be examined regularly for clinical or laboratory signs of a change in thyroid function. If there is a suspicion of a thyroid dysfunction, the serum TSH should be determined (using an ultrasensitive TSH assay).

Patients who received antiarrhythmics for a long time reported cases of increased ventricular defibrillation and / or an increase in the threshold of activation of a pacemaker or an implanted defibrillator, which may reduce the effectiveness of these devices. Therefore, before starting or during treatment with Cordarone®, regular checks should be made to ensure that they function correctly.

Regardless of the presence or absence of pulmonary symptoms during the treatment with Cordarone®, it is recommended to perform an X-ray examination of the lungs and pulmonary functional tests every 6 months. Deviations from the norm of the concentration of thyroid hormones.Because Cordarone® contains iodine, its administration can disrupt the absorption of radioactive iodine and distort the results of the radioisotope study of the thyroid gland, however, the administration of the drug does not affect the reliability of the determination of the free T3, T4, TTG concentration (using the ultrasensitivity method for determining TSH concentration) in blood serum.

Kordarone ® inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and can cause isolated biochemical changes (increase in serum free T4, with a slightly decreased or even normal serum free T3 concentration) in clinically euthyroid patients, which is not is the cause for the withdrawal of Cordarone®.

The development of hypothyroidism can be suspected at the appearance of the following clinical signs, usually mildly expressed: weight gain, cold intolerance, decreased activity, pronounced bradycardia (see section "Side effect"). The diagnosis is confirmed by a clear increase in the concentration of TSH in the blood serum, determined with the help of an ultrasensitive method for determining the concentration of TSH.

Normalization of thyroid function is usually observed within 1-3 months after discontinuation of treatment. In life-threatening situations, Cordarone® treatment can be continued with simultaneous additional use of L-thyroxin under the control of serum TSH concentration.

General and local anesthesia

Before surgery, the anesthetist should be informed that the patient is taking Cordarone®.

Against the background of taking Cordarone®, it is possible to increase the hemodynamic risks inherent in local or general anesthesia (in particular, this is related to a decrease in heart rate, a slowing of conduction and a decrease in heart contractility).

Effect on the ability to drive transp. cf. and fur:

Based on safety data, there is no evidence that amiodarone violates the ability to drive vehicles or engage in other potentially hazardous activities. However, as a precautionary measure patients with paroxysms of severe rhythm disturbances during the treatment with Cordarone® should preferably refrain from driving and potentially exercisingdangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets 200 mg.

Packaging:10 tablets per blister PVC / Al. For 3 blisters together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014833 / 02

Date of registration:27.01.2009

The owner of the registration certificate:Sanofi-Aventis FranceSanofi-Aventis France France

Manufacturer: & nbsp

SANOFI WINTHROP INDUSTRIE France

Representation: & nbspSanofi Russia, JSCSanofi Russia, JSCRussia

Information update date: & nbsp13.04.2015

Illustrated instructions

Instructions

Cordarone® (Cordarone® )