Amiocordin - instructions for use, dose, side effects, contraindications

Excipients: Lactose monohydrate 93.00 mg corn starch 36.00 mg, 14.00 mg of povidone, colloidal silicon dioxide, anhydrous 2.40 mg Magnesium stearate 4.60 mg.

Description:

Round, biconvex tablets from white to slightly cream colored, with a risk on one side.

Pharmacotherapeutic group:Antiarrhythmic drug

ATX: & nbsp

C.01.B.D.01 Amiodarone

Pharmacodynamics:

Amiodarone refers to III class antiarrhythmic agents (repolarization inhibitors class) and has a unique mechanism of antiarrhythmic action, because in addition to the properties of III class antiarrhythmics (potassium channel blockade) it possesses antiarrhythmic I class effects (sodium channel blockade), antiarrhythmics IV class (calcium channel blockade) and noncompetitive beta adrenoblocking action.

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

Antiarrhythmic properties:

- prolongation of the third phase of the action potential of cardiomyocytes, mostly by blocking the potassium ion current in the channels (III antiarrhythmic effect class Williams classification);

- a decrease in the automatism of the sinus node, which leads to a decrease in the frequency of the coresMr.th abbreviations;

- 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 of 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 triiodothyronine (T₃) in thyroxine (T₄) (blockade of thyroxine-5-deiodinase) and blocking the seizure of these hormones by cardiomyocytes 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 concentrations in the blood plasma are reached after 3-7 hours. However, the therapeutic effect usually develops a 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 by 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 under conditions 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 (POC2). In conditions in vivo the interaction of amiodarone with substrates of 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 through the intestine. Amiodarone and its metabolites are not excreted by hemodialysis. Amiodarone has a long half-life (T₁_/₂) with a large individual variability (so when choosing a dose, for example, increasing or decreasing it, it should be remembered that at least 1 month to stabilize the new plasma concentration of amiodarone).

Excretion during ingestion proceeds in 2 phases: initial T_1/2(first phase) - 4-21 hours, T_1/2in the second phase - 25-110 days. After a long oral administration, an average T_1/2-40 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 the 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 amiodarone is excreted through the intestine after passing through the liver, but with prolonged administration of amiodarone, iodine concentrations 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 different patient groups

Impaired renal function

Due to the insignificant removal of amiodarone by the kidneys, patients with renal insufficiency do not need a dose adjustment of amiodarone.

Indications:

Relapse prevention:

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

- supraventricular 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 with recent myocardial infarction who have more 10 ventricular extrasystoles in 1 hour, clinical manifestations of chronic heart failure and a reduced fraction of left ventricular ejection (less than 40%).

The drug Amiocordin ® can be used in the treatment of rhythm disturbances in patients with coronary heart disease and / or violations of the function of the left ventricle.

Contraindications:

- Hypersensitivity to iodine, amiodarone or excipients of the drug.

- Lactose intolerance, 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 block II-III degree, in the absence of the patient's installed artificial pacemaker (pacemaker).

- Hypokalemia, hypomagnesemia.

- Simultaneous use with drugs that can lengthen the interval QT and cause the development of paroxysmal tachycardia,including ventricular tachycardia of the "pirouette" type (see section "Interaction with other drugs"):

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

- Congenital or acquired lengthening interval QT.

- Thyroid dysfunction (hypothyroidism, hyperthyroidism).

- Interstitial lung disease.

- Pregnancy (except in special cases, see the section "Application during pregnancy and during breastfeeding").

- The period of breastfeeding (see the section on "Application during pregnancy and during breastfeeding").

- Age under 18 years (efficiency and safety not established).

Carefully:

In decompensated or severe chronic heart failure (III-IV functional class by classification NYHA), hepatic insufficiency, bronchial asthma, severe respiratory failure, in elderly patients (high risk of severe bradycardia), with atrioventricular blockade 1 degree.

Pregnancy and lactation:

Pregnancy

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 when the drug is used after thisperiod may 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 contraindicated during pregnancy, except in special cases when the expected benefit exceeds the risk (in case of life-threatening ventricular arrhythmias).

Breastfeeding period

Amiodarone is excreted in breast milk in significant amounts, so it is contraindicated during breastfeeding (it is necessary to cancel the drug or stop breastfeeding).

Dosing and Administration:

The drug Amiocordin ® should be taken only as prescribed by a doctor!

Amiocordin® 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 to 800 mg (to a maximum of 1200 mg) per day until a total dose of 10 g is reached (usually within 5 to 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 is reached (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 the drug Amiocordin ® has a very long half-life, it can be taken every other day or take breaks in its reception 2 day in 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.

Elderly patients

In the treatment of elderly patients, the lowest loading and maintenance doses of Amyocordin® are recommended.

Side effects:

The incidence of adverse events was determined in accordance with the World Health Organization (WHO) classification: 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 of the blood and lymphatic system:

very rarely: hemolytic anemia, aplastic anemia, thrombocytopenia;

frequency unknown: neutropenia, agranulocytosis.

Heart Disease:

often: a bradycardia, usually mild and dose-dependent;

infrequently: arrhythmogenic action (occurrence of new rhythm disturbances or weighting of existing rhythm disturbances, in some cases with subsequent cardiac arrest) (see section "Interaction with other drugs");

very rarely: severe bradycardia or arrest of the sinus node in patients with sinus node dysfunction and / or elderly patients;

frequency is unknown: conduction disorders (sinoatrial block, atrioventricular block 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.

Disturbances on the part of the organ of sight:

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;

frequency 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: an isolated increase in the activity of transaminases in the blood serum, usually mild (exceeding the upper limit of the norm (VGN) from 1.5 to 3 times), observed at the beginning of treatment. The activity of "liver" 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.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;

Frequency unknown: Parkinsonism, parosmia (odor disorder, especially subjective perception of odor, objectively absent).

Disorders of the psyche:

frequency unknown: state of confusion / delirium, hallucinations.

Violation of the genitals and mammary gland:

Very rarely: epididymitis, impotence; frequency is unknown: decreased libido.

Disturbances from the respiratory system, chest and mediastinal organs:

often: pulmonary toxicity (alveolar / interstitial pneumonitis or fibrosis, pleurisy, obliterating bronchiolitis with arranging pneumonia [cryptogenic organizing 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 medicinal products ");

frequency unknown: pulmonary hemorrhage.

Disturbances from the skin and subcutaneous tissues:

very often: photosensitization;

often: in the case of prolonged use of amiodarone in high daily doses, grayish or bluish skin pigmentation may be observed, after the cessation of treatment this pigmentation slowly disappears;

very rare: during the radiation therapy may occur cases of erythema, skin rash, usually nonspecific, exfoliative dermatitis, alopecia;

frequency unknown: eczema, urticaria, severe skin reactions, sometimes fatal, including toxic epidermal necrolysis / Stevens-Johnson syndrome, bullous dermatitis, drug reaction with eosinophilia and systemic symptoms.

Vascular disorders:

very rarely: vasculitis.

Overdose:

When administered to 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, the use of activated charcoal (if the drug is taken recently), in the remaining cases, symptomatic therapy is performed: with bradycardia, beta-adrenostimulators or pacemaker installation, with ventricular pirouette tachycardia - intravenous 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 bi-directional ventricular tachycardia such as "pirouette" or increase the duration of the interval QT

Medicines that can cause ventricular tachycardia such as "pirouette"

Combination therapy with drugs that can cause ventricular pirouette tachycardia is contraindicated, as it increases the risk of potentially lethal ventricular pirouette tachycardia. These include:

antiarrhythmic drugs: IA class (quinidine, hydroquinidine, disopyramide, procainamide), sotalol;
other (non-antiarrhythmic) drugs, such as beprideal, wincamine, some neuroleptics: phenothiazines (chlorpromazine, ciammazin, levomenromazine, 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 drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine), pentamidine for parenteral administration, dipemannyl methyl sulfate, misolastine, astemizole, terfenadine.

Drugs that can increase the duration of the interval QT

Simultaneous reception of amiodarone with drugs that can increase the duration of the interval QT, 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 ventricular pirouette tachycardia) (see "Special instructions"), when using such combinations, it is necessary to constantly monitor the patient's electrocardiogram (ECG) for elongation of the interval QT), 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

Uncommon combinations:

with laxatives, stimulating intestinal motility, which can cause hypokalemia, increasing the risk of developing a ventricular pirouette tachycardia. Simultaneously with amiodarone, laxatives of other groups should be used.

Combinations requiring caution when used:

with diuretics causing hypokalemia (in monotherapy or in combination with other drugs);
with systemic corticosteroids (glucocorticosteroids, mineralocorticosteroids), tetracosactide;
with amphotericin B (intravenous administration).

It is necessary to prevent the development of hypokalemia, and in case of its occurrence, to restore to normal values the content of potassium in the blood, to control the content of electrolytes in the blood and the ECG (for possible lengthening of the interval QT) And in the case of ventricular tachycardia type "pirouette" should not apply antiarrhythmics (ventricular pacing, intravenous administration may magnesium salts) should be initiated.

Medicines for general anesthesia

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

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

Medicines that reduce heart rate (clonidine, guanfacine, cholinesterase inhibitors [donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide], pilocarpine)

The risk of developing excessive bradycardia (cumulative effects).

Influence of amiodarone on other drugs

Amiodarone and / or its metabolite desethylamiodarone inhibit isoenzymes CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-gp and can increase the systemic exposure of medicines that are their substrates. In connection with the long T_1/2amiodarone, this interaction can be observed even a few months after discontinuation of its administration.

Medicines that are substrates P-gp

Amiodarone is an inhibitor P-gp. It is expected that its simultaneous reception with drugs that are 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, with simultaneous use of digoxin 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.

Medicines that are the substrates of the isoenzyme CYP2C9

Amiodarone increases the concentration in the blood of drugs that are substrates of the isoenzyme CYP2C9, such as warfarin 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

With the simultaneous use of phenytoin with amiodarone, the development of an overdose of phenytoin may occur, which may lead to the appearance of neurological symptoms. Clinical monitoring and reduction of the dose of phenytoin is necessary at the first signs of overdose, it is desirable to determine the concentration of phenytoin in the blood plasma.

Medicines that are the substrates of the isoenzyme CYP2D6

Flecainide

Amiodarone increases the plasma concentration of flecainide by inhibiting the isoenzyme CYP2D6, in connection with which correction of doses of flecainide is required.

Medicines that are the substrates of the isoenzyme CYP3A4

With the simultaneous use of amiodarone, an inhibitor of isoenzyme 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

Simultaneous use of cyclosporine with amiodarone may increase the concentration of cyclosporine in the blood plasma, 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 lovastatin)

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

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 isoenzymes CYP2D6 and CYP3A4

Dextromethorphan

Amiodarone inhibits isoenzymes CYP2D6 and CYP3A4 and theoretically can 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

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

Recommended to avoid admission inhibitors of isoenzyme CYP3A4 (eg, grapefruit juice and some medicines, such as cimetidine and HIV protease inhibitors (v.h. indinavir)) during treatment with amiodarone. HIV protease inhibitors, when used simultaneously with amiodarone, can increase the concentration of amiodarone in the blood.

Inductors of isoenzyme CYP3A4

Rifampicin

Rifampicin is a strong inducer of isoenzyme CYP3A4, when used simultaneously with amiodarone, it can reduce the plasma concentrations of amiodarone and desethylamiodarone.

Preparations of St. John's Wort

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

Special instructions:

The side effects of Amyocordin® are usually dose-dependent, so minimal effective doses should be used to minimize the possibility of their occurrence.

Patients should be warned that,so that during treatment they avoid exposure to direct sunlight or take protective measures (for example, applying sunscreen, wearing appropriate clothing).

Reactions from the heart

The pharmacological action of Amyocordin® causes ECG changes: lengthening of the interval QT, QT_c (corrected), associated with the lengthening of the period of repolarization of the ventricles of the heart, with the possible appearance of waves U. However, these changes are not a manifestation of the toxic effect of Amyocordin®. It is possible to increase the interval QT_C no more than 450 ms or no more than 25% of the original value.

In elderly patients, a significant slowdown in heart rate is possible. With the development of atrioventricular blockade II and III degree, sinoatrial blockade or a two-beam intraventricular blockade, treatment with Amyocordin® 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 fatal outcome.It is very important, but difficult, to make a differential diagnosis between insufficient effectiveness of the drug and its arrhythmogenic effect, whether or not combined with an aggravation of the severity of the cardiovascular pathology. When using the drug Amiocordin ® on arrhythmogenic action was reported significantly less often than with the use of other antiarrhythmic drugs and, as a rule, it was observed in the presence of factors that increase the duration of the interval QT, such as interaction with other drugs and / or impaired electrolyte content in the blood (see "Side effects" and "Interaction with other drugs" sections). Despite the ability of the drug Amiocordin® to increase the duration of the interval QT, he showed low activity with respect to provoking ventricular tachycardia of the "pirouette" type.

Hyperthyroidism (see section "Side effect").

Amyocordin® preparation or during several months after its termination, hyperthyroidism may develop. Clinical manifestations are usually mild, so symptoms such as weight loss,the occurrence of rhythm disturbances, attacks of angina pectoris, the development of chronic heart failure should alert the doctor. The diagnosis is confirmed by the detection of a decrease in the concentration of thyroid-stimulating hormone (TSH) in the serum, determined with the help of ultrasensitive analysis on TSH. In this case, the drug Amiocordin® 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 effective), glucocorticosteroids, beta-adrenoblockers.

Neuromuscular disorders (see section "Side effect")

Amiocordin® can cause peripheral sensory-motor neuropathy and / or myopathy.

Recovery usually occurs within a few months after the withdrawal of Amyocordin® 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, the drug Amiocordin^® It is necessary to cancel 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 need for Amyocordin® should be reassessed, as with its early cancellation, interstitial pneumonitis is usually reversible (clinical symptoms are usually resolved within 3-4 weeksfollowed by a slower improvement in the radiographic pattern and function of the lungs for several months). Consideration should be given to the treatment of glucocorticosteroids.

Moreover, in very rare cases, usually in the immediate after surgery, a serious complication from the respiratory system (acute adult respiratory distress syndrome) was observed, sometimes fatal, it is supposed that its development can be linked with interaction with high concentrations of oxygen (see section "Side effect").

Disorders from the side of the liver

It is recommended to carefully monitor the functional "liver" tests (monitoring the activity of "liver" transaminases) before starting the use of Amyocordin® and regularly during treatment with the drug. When taking Amyocordin ®, acute liver function abnormalities (including hepatocellular insufficiency or liver failure, sometimes fatal) and chronic liver damage are possible. Therefore, with an increase in the activity of "liver" transaminases, 3 times higher BGI, the dose of Amyocordin® should be reduced or stopped.

Clinical and laboratory signs of chronic liver failure with Amyocordin® oral administration can be minimally expressed (hepatomegaly, increased transaminase activity 5 times higher than UGN) and reversible after drug withdrawal, however, deaths have been reported.

Severe bullous reactions

Amiocordin® should be discontinued immediately if symptoms and manifestations of life-threatening or even fatal reactions appear in the form of Stevens-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 Amyocordin® with the following drugs: beta-adrenoblockers, blockers of "slow" calcium channels, which cut heart rate (verapamil, diltiazem), stimulating peristalsis of the intestines with laxatives, which can cause hypokalemia.

Monitoring of treatment

Before starting Amyocordin®, it is recommended that an ECG and a serum potassium test be performed.

Hypokalemia should be corrected before starting Amyocordin®. 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, due to the fact that Amyocordin® can cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, a clinical and laboratory examination should be conducted before the reception of Amyocordin® for abnormalities in thyroid function (concentration of TSH in the thyroid gland serum, determined by the use of ultra-sensitive analysis on TSH). During treatment with Amiocordin® and several months after discontinuation, the patient should be regularly examined 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 Amiocordin®, regular checks should be made to ensure that they function correctly.

Regardless of the presence or absence during the treatment with Amyocordin®, the pulmonary symptoms are recommended every 6 months to conduct X-ray examination of lungs and pulmonary functional tests.

Deviations from the norm of the concentration of thyroid hormones

Because Amyocordin® contains iodine, its administration can disrupt the absorption of radioactive iodine and distort the results of a radioisotope study of the thyroid gland, but the administration of the drug does not affect the reliability of determining the concentration of free T₃, T₄ and TSH (using an ultrasensitive method for determining the concentration of TSH) in the blood serum. Amiocordin® inhibits peripheral T₄ in T₃ and can cause isolated biochemical changes (increase in the concentration of free T₄ in the blood serum, with a slightly reduced or even normal concentration of free T₃ in the blood serum) in clinically euthyroid patients, which is not a reason to discontinue Amyocordin®.

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, treatment with Amyocordin® can be continued with simultaneous additional use L-tiroxine under the control of serum TSH concentration.

General and local anesthesia

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

Amyocordin® may cause an increase in hemodynamic risks, inherent in local or general anesthesia, especially with regard to cardiac arrhythmia, conduction slowdown and reduced 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 for patients with paroxysms of severe rhythm disturbances during the treatment with Amiocordin®, it is advisable to refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, 200 mg.

Packaging:

For 10 tablets in a blister of PVC / aluminum foil.

By 3, 6 or 50 blisters are placed in a pack of cardboard along with the instructions for use.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N011617 / 01

Date of registration:23.12.2009 / 11.11.2015

Expiration Date:Unlimited

Date of cancellation:2017-09-13

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp13.09.2017

Illustrated instructions

Instructions

Amiocordin® (Amiokordin®)