Aritmil tablets 200 mg blister No. 20

Instructions for use Aritmil tablets 200 mg blister No. 20

Composition

active ingredient: amiodarone hydrochloride;

1 tablet contains 200 mg of amiodarone hydrochloride (calculated on a 100% dry substance);

Excipients: corn starch, microcrystalline cellulose, calcium stearate, povidone, lactose monohydrate.

Dosage form

Pills.

Main physicochemical properties: round tablets, white or almost white in color, with a flat surface with beveled edges and a score.

Pharmacotherapeutic group

Cardiological drugs. Class III antiarrhythmic drugs. ATX code C01B D01.

Pharmacological properties

Pharmacodynamics

Class III antiarrhythmic drug. The antiarrhythmic effect is due to an increase in the 3rd phase of the action potential, mainly due to the blockade of potassium channels of cardiomyocyte membranes, as well as calcium channels, slowing down conduction through the AV node and reducing the automaticity of the sinus node. To a small extent, it blocks open and inactivated sodium channels and slows down the fast inward sodium flow. The drug non-competitively blocks alpha- and beta-adrenoreceptors mainly of the myocardium, which also contributes to the slowing down of sinoatrial, atrial and AV conduction, without affecting intraventricular conduction. Amiodarone increases the refractory period and reduces myocardial excitability. Slows down the conduction of excitation and prolongs the refractory period of additional atrioventricular pathways. The antianginal effect of amiodarone is due to a decrease in myocardial oxygen consumption by reducing heart rate and total peripheral vascular resistance. Amiodarone does not cause a significant negative inotropic effect.

Pharmacokinetics

Amiodarone has a large volume of distribution. In the first days of administration, the drug accumulates in almost all tissues, especially in fatty inclusions, liver, spleen, lungs. After a few days, amiodarone is eliminated from the body. Stable concentration is achieved within 1 to several months, depending on the individual characteristics of the patient. Amiodarone is excreted in bile and feces. Renal excretion is insignificant. The half-life is 20-100 days. After cessation of treatment with amiodarone, its elimination from the body continues for several months. Amiodarone contains iodine, so during metabolism in the liver, iodine is cleaved and excreted in the urine in the form of salts. The main part of amiodarone and its metabolites are excreted through the intestines for more than 30 days. After discontinuation of the drug, its effective effect lasts for several days or even weeks.

Indication

Prevention of relapses:

· ventricular tachycardia, which poses a threat to the patient's life: treatment must be started in a hospital setting with constant monitoring of the patient's condition;

· symptomatic ventricular tachycardia (documented) that leads to incapacity;

· supraventricular tachycardia (documented) requiring treatment, and in cases where other drugs have no therapeutic effect or are contraindicated;

· ventricular fibrillation.

Treatment of supraventricular tachycardia: slowing or reducing atrial fibrillation or flutter.

Ischemic heart disease and/or left ventricular dysfunction (see section "Pharmacodynamics").

Contraindication

Hypersensitivity to iodine and/or amiodarone, to other components of the drug;

· sinus bradycardia (< 50-55 beats/min), sinoatrial block, sick sinus syndrome in the absence of an artificial pacemaker (risk of sinus node arrest);

· severe conduction disorders (II and III degree AV block, bifascicular or trifascicular block) in the absence of an artificial pacemaker;

Thyroid dysfunction (hypothyroidism, hyperthyroidism). Thyroid function should be checked in all patients before starting treatment;

· simultaneous use with drugs that can cause polymorphic ventricular tachycardia of the torsade de pointes type:

- class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);

- class III antiarrhythmic drugs (sotalol, dofetilide, ibutilide);

- other drugs such as arsenic compounds, bepridil, cisapride, diphemanil, dolasetron (intravenously), erythromycin (intravenously), mizolastine, moxifloxacin, spiramycin (intravenously), vincamine (intravenously), toremifene, some neuroleptics (for details see the section "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions

Due to the long half-life of amiodarone, the possibility of interaction exists not only with concomitant therapy with other drugs during treatment, but also for several months after discontinuation of amiodarone.

The most significant interactions of amiodarone are with oral anticoagulants, digoxin, phenytoin, and drugs that prolong the QT interval.

· Antiarrhythmic drugs.

Myocardial depression increases with the concomitant use of several antiarrhythmic drugs.

Oral anticoagulants.

Amiodarone increases plasma concentrations of oral anticoagulants (including warfarin) due to inhibition of CYP2C9. The enhanced effect of oral anticoagulants with an increased risk of bleeding dictates the need for more frequent monitoring of prothrombin levels in the blood and correction of anticoagulant doses during treatment with amiodarone and for 8 days after drug withdrawal.

Phenytoin (fosphenytoin).

It is possible to increase the plasma level of phenytoin (due to inhibition of CYP2C9) with the development of symptoms of overdose (in particular, neurological). Clinical monitoring and reduction of the dose of phenytoin are necessary if signs of overdose appear; if possible, determination of the level of phenytoin in the blood plasma.

· Cardiac glycosides (digitalis preparations).

Possible disturbances of automaticity (marked bradycardia) and atrioventricular conduction (synergism of action); possible increase in plasma digoxin concentration (due to reduced clearance) and increased risk of digoxin toxicity.

Clinical, electrocardiographic and laboratory monitoring (if possible, determination of digoxin plasma levels) is necessary for early detection of signs of glycoside intoxication; it may be necessary to halve the digoxin dose.

The simultaneous use of two drugs, each of which contributes to the occurrence of ventricular tachycardia of the torsade de pointes type, is usually contraindicated.

However, methadone and some antiparasitic drugs (halofantrine, lumefantrine, pentamidine) are exceptions to this rule and are not recommended for use with other drugs that contribute to the occurrence of torsade de pointes-type ventricular tachycardia.

Combination therapy with the following drugs is contraindicated due to QT prolongation and increased risk of torsade de pointes:

Class IA antiarrhythmic drugs, e.g. quinidine, hydroquinidine, procainamide, disopyramide;

Class III antiarrhythmic drugs, such as dofetilide, ibutilide, sotalol, bretylium;

· other drugs that do not have antiarrhythmic activity, including macrolide antibiotics (erythromycin for intravenous administration, spiramycin), co-trimoxazole for parenteral administration, vincamine (intravenously), cisapride, bepridil, arsenic compounds, diphemanil, dolasetron (intravenously);

· some antipsychotics (chlorpromazine, cyamemazine, levopromazine, thioridazine, trifluoperazine, amisulpride, sulpiride, tiapride, veralipride, droperidol, fluphenazine, haloperidol, pimozide, pipamperon, pipotiazine, sertindole, sultopride, trazodone, zuclopenthixol);

Lithium and tricyclic antidepressants, such as doxepin, maprotiline, amitriptyline;

· some antihistamines, for example, loratadine, terfenadine, astemizole, mizolastine;

· antimalarial drugs, e.g. quinine, mefloquine, chloroquine;

· moxifloxacin, sparfloxacin, toremifene.

Fluoroquinolones

Cases of QT prolongation with/without torsade de pointes have been reported when amiodarone was administered with fluoroquinolones. Concomitant use of amiodarone with fluoroquinolones should be avoided (combination with moxifloxacin, sparfloxacin is contraindicated, see above). If such a combination is unavoidable, careful prior monitoring of the QT interval and continuous ECG monitoring are necessary.

Combination therapy with the following drugs is not recommended:

Beta-blockers, except sotalol (contraindicated combination) and esmolol (combination requires precautions when used), and some calcium channel inhibitors that reduce heart rate (diltiazem, verapamil): possible potentiation of negative chronotropic effects and slowing of conduction with the development of pronounced bradycardia, AV block, increased risk of ventricular arrhythmias, especially "torsade de pointes". If such a combination is unavoidable, careful preliminary control of the QT interval and constant ECG monitoring during treatment are necessary;

Stimulant laxatives, which can lead to hypokalemia, thereby increasing the risk of torsade de pointes; other types of laxatives should be used;

· HIV protease inhibitors: amiodarone is metabolized by cytochrome P450 isoenzymes CYP3A4 and CYP2C8, therefore interactions with inhibitors of these enzymes, in particular CYP3A4 inhibitors, such as HIV protease inhibitors, are possible. The combination may lead to inhibition of amiodarone metabolism, increase its concentration and increase the risk of serious side effects (e.g. arrhythmias). Such a combination should be avoided. If such a combination is necessary, the patient's condition should be carefully monitored;

· methadone: increased risk of ventricular arrhythmias, particularly torsade de pointes. ECG monitoring and clinical monitoring are necessary.

Combination therapy with the following drugs requires precautions:

Other drugs that may cause hypokalemia and thus increase the risk of torsade de pointes:

- diuretics, alone or in combination;

- systemic glucocorticoids and mineralocorticoids, tetracosactide;

Hypokalemia should be prevented and corrected as necessary, and electrolyte levels, QT interval, and ECG U waves should be monitored. An increase in the QT interval to 450 ms or no more than 25% of baseline is acceptable.

In the event of paroxysmal tachycardia of the torsade de pointes type, antiarrhythmic drugs should not be used, but ventricular pacing should be performed to reduce the heart rate, and intravenous administration of magnesium preparations is possible.

General anesthesia or high-dose oxygen therapy

- Cases of severe complications in patients undergoing general anesthesia have been described: bradycardia that is not corrected by atropine, arterial hypotension, conduction disturbances, decreased cardiac output;

- rare cases of severe respiratory complications, sometimes fatal (adult acute respiratory distress syndrome), have been observed usually in the early postoperative period, possibly due to interaction with high oxygen concentrations during forced ventilation.

· Esmolol

Possible impairment of automaticity, conduction and contractility of the heart due to suppression of sympathetic compensatory mechanisms. Clinical and electrocardiographic monitoring of the patient's condition is necessary.

Other drugs that cause bradycardia

In addition to the beta-blockers mentioned above, in addition to sotalol (contraindicated combination), calcium channel blockers, cardiac glycosides, amiodarone interacts with clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambemonium, pyridostigmine, neostigmine), pilocarpine with an increased risk of excessive bradycardia (additive effects), ventricular arrhythmias, especially paroxysmal tachycardia of the torsade de pointes type. Clinical and electrocardiographic monitoring of the patient's condition is recommended.

· P-glycoprotein substrates, including dabigatran: since amiodarone is a P-glycoprotein inhibitor, concomitant use may increase the concentration of P-glycoprotein substrates in the blood and the risk of their adverse reactions. With increasing plasma concentrations of dabigatran, the risk of bleeding increases, therefore clinical monitoring and dose adjustment of dabigatran (not higher than 150 mg/day) are necessary.

· Drugs metabolized by the cytochrome P450 3A4 system

It is possible to increase the concentration of these drugs in the blood plasma due to inhibition of their metabolism in the liver and, as a result, it is possible to increase their pharmacodynamic effects and/or toxicity, which may require a reduction in their doses:

- cyclosporine: a 2-fold increase in cyclosporine levels in blood plasma is possible; dose adjustment is necessary to maintain therapeutic drug concentrations in blood plasma;

- fentanyl: amiodarone may potentiate the effects of fentanyl, thereby increasing the risk of its toxicity;

- theophylline: increased theophylline concentration in the blood with an increased risk of developing its adverse reactions;

- bupivacaine, levobupivacaine, prilocaine, ropivacaine, lidocaine: specific studies of the interaction of local anesthetics with class III antiarrhythmic drugs (e.g. amiodarone) have not been conducted, but caution is recommended with such a combination - the patient's condition and ECG should be carefully monitored, as the risk of myocardial depression increases;

- macrolides (e.g. clarithromycin, azithromycin, roxithromycin): this combination should be based on a careful assessment of the potential risks and benefits for each patient due to the increased risk of ventricular arrhythmias, in particular torsade de pointes; ECG monitoring and clinical monitoring of the patient are necessary during concomitant use of these drugs;

- orlistat: possible decrease in plasma levels of amiodarone and its active metabolites. Clinical monitoring, ECG monitoring are necessary; amiodarone dose adjustment may be necessary;

- statins metabolized by CYP3A4 (including simvastatin, atorvastatin, lovastatin): dose-dependent increase in the risk of rhabdomyolysis. In the case of simvastatin, its dose should not exceed 20 mg per day. If the therapeutic effect is not achieved when using the drug in this dose, another statin that does not interact with amiodarone should be prescribed;

- other drugs metabolized by CYP3A4: tacrolimus (risk of nephrotoxicity), sildenafil (risk of increased side effects), triazolam, midazolam (risk of psychomotor effects), dihydroergotamine, ergotamine, colchicine; dose adjustment is necessary.

· H2-histamine receptor antagonists (cimetidine), azole antifungals (ketoconazole, itraconazole), telithromycin inhibit CYP3A and may increase blood levels of amiodarone, increasing the risk of ventricular arrhythmias.

· Clopidogrel: Since clopidogrel is metabolized by CYP3A4 in the liver to its active form, concomitant use of amiodarone may result in ineffective inhibition of platelet aggregation.

Grapefruit juice inhibits cytochrome P450 3A4, which may lead to increased plasma concentrations of amiodarone. Its use should be avoided during treatment with amiodarone.

Interaction with other substrates of cytochrome P450 isoenzymes: in vitro studies have shown that amiodarone is also an inhibitor of CYP 1A2, CYP 2C19 and CYP 2D6 through its main metabolite. Amiodarone may increase plasma concentrations of drugs whose metabolism depends on CYP 1A2, CYP 2C19 and CYP 2D6, e.g. dextromethorphan, metoprolol.

Application features

Patients with rare hereditary problems of galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome should not take the drug due to its lactose content.

Amiodarone can cause serious adverse reactions from the organs of vision, heart, lungs, liver, thyroid gland, skin, peripheral nervous system. Since the onset of these reactions may be delayed in time, the condition of patients with long-term treatment should be carefully monitored. Given that undesirable effects are dose-dependent, minimal effective doses should be used for maintenance therapy.

Cardiac effects and electrolyte imbalances

The drug should be used with caution in elderly patients, patients receiving cardiac glycosides, due to the risk of developing severe bradycardia, severe conduction disturbances with possible occurrence of idioventricular rhythm, especially when using high doses. If such conditions occur, treatment with the drug should be discontinued, beta-adrenomimetics or glucagon may be used, and if necessary, cardiac pacing. Given the long half-life of amiodarone, in severe bradycardia it is advisable to consider the possibility of connecting an artificial pacemaker.

The use of amiodarone tablet form is not contraindicated in latent or manifest heart failure, but caution should be exercised, as existing heart failure may worsen. In such cases, Aritmil should be used in combination with appropriate drugs.

Against the background of amiodarone treatment, ECG changes are possible: prolongation of the QT interval (due to prolonged repolarization) with the appearance of a U wave and deformation of the T wave. These changes are not a manifestation of drug toxicity.

In elderly patients, a significant decrease in heart rate is possible.

Treatment with the drug should be discontinued in the event of second or third degree AV block, sinoatrial block, or bifascicular block.

Amiodarone has a low proarrhythmic effect, which is manifested mainly when used with drugs that prolong the period of ventricular repolarization or in cases of electrolyte imbalance (especially hypokalemia). Cases of new or exacerbation of existing arrhythmias have been reported during treatment with amiodarone, sometimes with a fatal outcome; it is important to take into account situations that may be associated with hypokalemia. Although amiodarone can cause prolongation of the QT interval, its ability to provoke paroxysmal ventricular tachycardia of the torsade de pointes type is insignificant.

Before starting treatment, each patient should have an ECG and determine the level of potassium in the blood plasma. Hypokalemia and other electrolyte imbalances should be corrected before starting amiodarone and ECG, blood electrolytes and clinical monitoring of the patient's condition should be carried out during the use of the drug.

Amiodarone may increase the defibrillation threshold and/or the pacing threshold in patients with implanted cardioverter-defibrillators or pacemakers, which may adversely affect the effectiveness of the device. Regular tests are recommended to ensure proper device function after initiating treatment with the drug or changing the dosage.

Endocrine effects

Amiodarone use may cause hyperthyroidism/hypothyroidism, especially in patients with a history of thyroid dysfunction (including a family history), in elderly patients. Therefore, careful clinical and laboratory evaluation of thyroid function should be performed before starting treatment, during treatment (every 6 months) and for several months after stopping treatment, especially in elderly patients, patients with a history of nodules, goiter or other thyroid dysfunction.

If thyroid dysfunction is suspected, serum TSH levels should be measured.

Amiodarone contains iodine (200 mg of the drug contains approximately 75 mg of iodine), so it may affect the results of tests for the accumulation of radioactive iodine in the thyroid gland, however, the interpretation of the results of thyroid function tests (levels of hormones fT3, fT4, TSH) remains possible.

Amiodarone inhibits the conversion of thyroxine (T4) to triiodothyronine (T3) in peripheral tissues and may cause isolated biochemical changes (increased fT4, slight decrease/normal serum fT3) in clinically euthyroid patients. In such cases, there is no reason to discontinue amiodarone treatment unless there is clinical or further laboratory (TSH) evidence of thyroid disease.

Euthyroidism is usually restored 1-3 months after discontinuation of amiodarone treatment.

In life-threatening situations, if hypothyroidism occurs, amiodarone treatment may be continued in combination with levothyroxine, the dose of which is adjusted according to thyroid hormone levels.

Hyperthyroidism may occur during treatment with amiodarone or several months after its discontinuation. The appearance of clinical signs such as unexplained weight loss, asthenia, anxiety, increased heart rate, development of arrhythmia, angina, heart failure, should be reported to the doctor immediately. Insufficient effectiveness of antianginal and/or antiarrhythmic drugs is also possible, and in elderly patients - the development of mental symptoms, even thyrotoxicosis. The diagnosis is confirmed by a significant decrease in TSH, an increase in serum T3 and a reduced production of TSH during a functional test with thyrotropin-releasing hormone. An increase in serum reverse T3 is also possible. In cases of confirmed hyperthyroidism, amiodarone therapy should be discontinued. Clinical recovery usually occurs within several months and is preceded by normalization of thyroid function tests. Fatal cases of hyperthyroidism have been reported.

In cases of severe thyroid hyperactivity, it is necessary to consider the feasibility of using antithyroid drugs (high doses are possible initially), if ineffective - in combination with high doses of corticosteroids (e.g., 1 mg/kg prednisolone) for several weeks.

Visual impairment

In case of deterioration of visual clarity or decrease in visual acuity, a complete ophthalmological examination, including examination of the fundus, should be performed immediately. Amiodarone should be discontinued in case of amiodarone-induced neuropathy and/or optic neuritis, as there is a risk of their progression to complete blindness. Annual ophthalmological examination is recommended in such patients.

Hepatobiliary effects

Amiodarone administration can cause various effects on the liver, including cirrhosis, hepatitis, jaundice and liver failure, sometimes fatal (mainly with long-term therapy, sometimes at the beginning of treatment, especially after intravenous administration of amiodarone). Therefore, before starting treatment, during treatment with Aritmil, it is recommended to regularly (every 6 months) check liver function (transaminase activity) for early detection of its damage.

At the beginning of treatment, an isolated increase in serum transaminase activity is possible, usually moderate (1.5-3 times higher than normal). Normalization of these indicators occurs with a decrease in the dose or even spontaneously.

Cases of acute liver injury with elevated serum transaminases and/or jaundice are possible; in such cases, treatment should be discontinued.

Chronic liver damage has been reported with long-term treatment with amiodarone. When amiodarone is used for more than 6 months, changes in laboratory parameters, which may be moderate (1.5-5 times increase in serum transaminases), and/or the appearance of clinical signs (possible hepatomegaly), should raise the possibility of chronic liver damage. Clinical and laboratory abnormalities usually resolve after discontinuation of the drug, but in rare cases, a fatal outcome has been reported. Histological findings may be consistent with pseudoalcoholic hepatitis or cirrhosis.

It is not advisable to drink alcohol during treatment with Aritmil, although there have been no reports of potentiation of negative effects on the liver.

Nervous system disorders

Amiodarone, when used for a long time, can cause peripheral sensorimotor neuropathy and/or myopathy, which are usually reversible after drug withdrawal. However, recovery may be incomplete, very slow, and may not occur until several months after drug withdrawal.

Pulmonary effects

The occurrence of dyspnea and/or nonproductive cough should be considered as a possible sign of pulmonary toxicity (hypersensitivity pneumonitis, alveolar/interstitial pneumonitis or fibrosis, pleurisy, bronchiolitis obliterans with pneumonia). The deterioration is usually gradual, but rapid progression is possible. Most cases have been reported with long-term therapy, only a few of them developed soon after the start of treatment. Fatal cases of pulmonary toxicity have been reported.

Pulmonary abnormalities are generally reversible upon early discontinuation of amiodarone, with or without corticosteroids. Clinical symptoms usually resolve within a few weeks, followed by a slower recovery of chest X-rays and lung function (over several months). Some patients may deteriorate despite discontinuation.

In rare cases, pleurisy associated with interstitial pneumonia may occur.

In patients with severe respiratory disorders, especially bronchial asthma, bronchospasm may occur in isolated cases.

Anesthesia

Isolated cases of acute respiratory distress syndrome, sometimes fatal, have been reported with amiodarone, usually in the immediate postoperative period. This may be due to interaction with high oxygen concentrations. Careful monitoring of such patients is recommended during mechanical ventilation.

Also, prolonged use of amiodarone may increase the risk of hemodynamic side effects associated with general or local anesthesia, such as bradycardia, hypotension, decreased cardiac output, and conduction disturbances.

Dermatological effects

Patients should be advised to avoid direct sunlight, UV radiation and to use sunscreen during therapy, as the skin may become overly sensitive to sunlight. This effect may persist for several months after discontinuation of the drug. In most cases, symptoms are limited to tingling, burning and erythema of exposed skin, but severe phototoxic reactions with blistering are possible.

Drug interactions (for details see the section "Interaction with other drugs and other types of interactions")

To prevent undesirable effects, concomitant therapy must be carefully prescribed, taking into account clinically significant interactions with amiodarone.

It is not recommended to use amiodarone with beta-blockers, some calcium channel blockers that reduce heart rate (verapamil, diltiazem), laxatives that stimulate intestinal motility and can cause hypokalemia, fluoroquinolones, and HIV protease inhibitors.

Also, when using amiodarone with flecainide simultaneously, due to the increase in plasma levels of the latter, it is necessary to reduce the dose of flecainide accordingly and carefully monitor the patient's condition.

During treatment with amiodarone, it is not recommended to consume grapefruit juice (risk of increasing amiodarone concentration in the blood).

Drug withdrawal

After discontinuation of treatment, therapeutic concentrations of amiodarone may persist in the blood for several weeks due to its long half-life. It should be noted that arrhythmias may recur after further reduction of amiodarone blood levels. Patients should be monitored regularly even after discontinuation of treatment.

Use during pregnancy or breastfeeding

Since amiodarone affects the fetal thyroid gland, the use of the drug during pregnancy is contraindicated, except in cases where the benefits of its administration outweigh the risks associated with it.

If, given the long half-life of amiodarone, a decision is made to discontinue the drug before planned conception, the ratio of the real risk of recurrence of life-threatening arrhythmias to the possible risks to the fetus should be weighed.

Amiodarone passes into breast milk in significant amounts, so breastfeeding is contraindicated during treatment with the drug.

Ability to influence reaction speed when driving vehicles or other mechanisms

The drug may adversely affect the reaction rate when driving vehicles or other mechanisms, especially in patients with amiodarone-induced disorders of the organs of vision and the nervous system.

Method of administration and doses

Adults.

A dose of satiety.

Treatment should usually be started with 200 mg (1 tablet) 3 times a day for 8-10 days, reducing the dose to 200 mg 2 times a day over the next week.

In some cases, higher doses (4-5 tablets per day) may be used at the beginning of treatment, which are always taken for a short period of time and under electrocardiographic monitoring.

Maintenance dose.

The minimum effective dose should be used, depending on the patient's response to the drug. After a loading period, the dose can be reduced to ½ tablet (100 mg) per day or 1 tablet (200 mg) every 2 days. Occasionally, the patient may require a higher maintenance dose (up to 2 tablets per day). The maintenance dose should be reviewed regularly.

Excessively high doses during maintenance therapy may cause side effects, which are thought to be related to high levels of amiodarone and its metabolites in body tissues.

The tablet form of the drug is used for stabilization of the condition and long-term treatment. The dosage regimen is determined by the doctor individually.

Elderly patients.

As with all patients, it is important to use the lowest effective dose. Elderly patients may be more sensitive to the effects of Aritmil even at normal doses. Particular attention should be paid to monitoring thyroid function.

Children

The safety and effectiveness of amiodarone in children have not been evaluated at this time, so its use in children is not recommended.

Overdose

Treatment: drug withdrawal, symptomatic therapy. In case of bradycardia, beta-adrenomimetics, atropine or glucagon preparations can be used, if necessary - cardiac pacing. In case of paroxysmal tachycardia "torsade de pointes" - intravenous administration of magnesium salts, cardiac pacing aimed at reducing the heart rate.

Taking into account the pharmacokinetic profile of amiodarone, it is recommended to monitor the patient's condition (especially cardiac activity) for a long time.

Amiodarone and its metabolites are not removed by dialysis.

Adverse reactions

Blood and lymphatic system.

· Hemolytic anemia, aplastic anemia, thrombocytopenia;

· There have been cases of bone marrow granulomas in patients taking amiodarone. The clinical significance of this is unknown.

Cardiovascular system.

Bradycardia, usually moderate and dose-dependent;

· development or worsening of arrhythmias (including torsade de pointes), sometimes with subsequent cardiac arrest, conduction disturbances (sinoatrial block, AV block of varying degrees) - mainly when used together with drugs that prolong the period of repolarization of the heart ventricles or with electrolyte balance disorders;

in some cases - pronounced bradycardia, in exceptional cases - sinus node arrest, requiring discontinuation of treatment, especially in patients with sinus node dysfunction and/or in elderly patients;

· vasculitis.

Endocrine system (see section "Special instructions").

Hypothyroidism, hyperthyroidism, sometimes fatal;

· syndrome of inappropriate antidiuretic hormone secretion (SIADH), especially if the drug is used concomitantly with drugs that can induce hyponatremia.

Organs of vision.

· Microdeposits in the corneal epithelium, usually in the area under the pupil, which are usually visible only during slit-lamp examination and manifest as a colored halo in bright light or blurred vision. Microdeposits on the cornea consist of a complex of lipid layers, disappear after discontinuation of the drug and do not require discontinuation of treatment;

· neuropathy/optic neuritis, which can lead to blindness (see section "Special warnings and precautions for use").

Digestive tract.

· Gastrointestinal disorders (nausea, vomiting, dysgeusia), which usually occur during the period of drug saturation and disappear when the dose is reduced.

Hepatobiliary system (see section "Special instructions").

Isolated increase in serum transaminase activity at the beginning of treatment, usually moderate (1.5-3 times higher than normal). Normalization of these indicators occurs with a decrease in the dose or even spontaneously;

· acute liver damage with high levels of serum transaminase activity and/or jaundice, including acute liver failure, sometimes fatal;

· chronic liver diseases (pseudoalcoholic hepatitis, cirrhosis), sometimes fatal.

Immune system.

· Angioedema;

· hypersensitivity reactions to any component of the drug.

Nervous system.

Extrapyramidal tremor (the occurrence of which may require dose reduction or discontinuation of the drug), nightmares, sleep disturbances;

· peripheral sensorimotor neuropathies and/or myopathies, usually reversible after drug withdrawal (see section "Special warnings and precautions for use");

· cerebellar ataxia (regresses after dose reduction or drug withdrawal), benign intracranial hypertension (pseudotumor cerebri), headache, vertigo.

Reproductive system.

Epididymitis, orchitis, impotence.

Urinary system.

Kidney damage.

Respiratory system.

Manifestations of toxic