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Antiarrhythmic drug. Amiodarone belongs to class III (a class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action, because in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (sodium channel blockade), class IV antiarrhythmics (calcium channel blockade) and non-competitive beta-adrenergic blocking action.
In addition to the antiarrhythmic action, the drug has antianginal, coronary dilating, alpha and beta adrenergic blocking effects.
an increase in the duration of the 3rd phase of the action potential of cardiomyocytes, mainly due to blocking the ion current in potassium channels (the effect of class III antiarrhythmics according to Williams classification);
decrease in the automatism of the sinus node, leading to a decrease in heart rate;
non-competitive blockade of α- and β-adrenergic receptors;
slowing down of sinoatrial, atrial and AV conduction, more pronounced in 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 AV node;
slowing down the conduction and increasing the duration of the refractory period in additional beams of AV conduction.
no negative inotropic effect when taken orally;
decrease in oxygen consumption by the myocardium due to a moderate decrease in TPR and heart rate;
an increase in coronary blood flow due to a direct effect on the smooth muscles of the coronary arteries;
maintenance of cardiac output by reducing pressure in the aorta and decreasing systemic vascular resistance;
influence on the metabolism of thyroid hormones: inhibition of the conversion of T3 to T4 (blockade of thyroxine-5-deiodinase) and blocking the capture of these hormones by cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium.
After the start of taking the drug inside, the therapeutic effects develop on average after a week (from several days to 2 weeks). After the termination of his reception, amiodarone is determined in blood plasma within 9 months. The possibility of maintaining the pharmacodynamic effect of amiodarone for 10-30 days after its withdrawal should be taken into account.
Bioavailability after oral administration in different patients ranges from 30% to 80% (mean value about 50%). After a single dose of amiodarone inside, Cmax in the blood plasma is achieved after 3-7 hours. However, the therapeutic effect usually develops a week after the start of the drug intake (from several days to 2 weeks).
Plasma protein binding is 95% (62% - with albumin, 33.5% - with beta-lipoproteins). Amiodarone has a large Vd. Amiodarone is characterized by a slow release into tissues and a high affinity for them. 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 using the isoenzymes CYP3A4 and CYP2C8. Its main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the main 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 have also been shown to inhibit certain transporters such as P-glycoprotein (P-gp) and organic cation transporter (OC2). Interaction of amiodarone with substrates of isoenzymes CYP3A4, CYP2C9, CYP2D6 and P-gp was observed in vivo.
The elimination of amiodarone begins in a few days, and the achievement of equilibrium between the intake and elimination of the drug (reaching Css) occurs after one to several months, depending on the individual characteristics of the patient. The main route of elimination of amiodarone is the intestine. Amiodarone and its metabolites are not excreted by hemodialysis. Amiodarone has a long T1/2 with great individual variability (therefore, when choosing a dose, for example, increasing or decreasing it, it should be remembered that it takes at least 1 month to stabilize the new plasma concentration of amiodarone).
Excretion when ingested occurs in 2 phases: initial T1/2 (first phase) - 4-21 hours, T1/2 in the 2nd phase - 25-110 days. After prolonged oral administration, the average T1/2 is 40 days. After discontinuation of the drug, complete elimination of amiodarone from the body may continue for several months.
Each dose of amiodarone (200 mg) contains 75 mg of iodine. Part of the iodine is released from the drug and is found in the urine in the form of iodide (6 mg per 24 hours with a daily dose of 200 mg amiodarone). Most of the iodine remaining in the composition of the drug is excreted through the intestine after passing through the liver, however, with prolonged use of amiodarone, the concentration of iodine in the blood can reach 60-80% of the concentration of amiodarone in the blood.
The peculiarities of the pharmacokinetics of the drug explain the use of loading doses, which is aimed at the rapid accumulation of amiodarone in the tissues, in which its therapeutic effect is manifested.
Pharmacokinetics in special clinical cases
Due to the insignificant excretion of the drug by the kidneys in patients with renal insufficiency, dose adjustment of amiodarone is not required.
Indications of the drug Cordaron®
Prevention of recurrence of
life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be started in a hospital with careful cardiac monitoring).
supraventricular paroxysmal tachycardia:
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;
of documented attacks of recurrent persistent supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome.
atrial fibrillation (atrial fibrillation) and atrial flutter.
Prevention of sudden arrhythmic death in high-risk
patients - patients after a recent myocardial infarction, having more than 10 ventricular extrasystoles in 1 hour, clinical manifestations of chronic heart failure and a reduced left ventricular ejection fraction (less than 40%).
Cordaron® can be used in the treatment of rhythm disturbances in patients with coronary artery disease and / or impaired left ventricular function.
The drug should be taken only as directed by a doctor.
Kordarontablets® taken orally before meals and drink plenty of water.
Loading ("saturating") dose: various saturation schemes can be applied.
In the hospital: the initial dose, divided into several doses, ranges from 600-800 mg (up to a maximum of 1200 mg) / day until a total dose of 10 g is reached (usually within 5-8 days).
Outpatient: 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: may vary in different patients from 100 to 400 mg / day. The minimum effective dose should be used in accordance with the individual therapeutic effect.
Because Cordaron® has a very large T1/2, it can be taken every other day or take breaks from taking it 2 days a week.
The average therapeutic single dose is 200 mg.
The average therapeutic daily dose is 400 mg.
The maximum single dose is 400 mg.
The maximum daily dose is 1200 mg.
Contraindications to the use
SSSU (sinus bradycardia, sinoatrial blockade), except for the cases of their correction by an artificial pacemaker (danger of "stopping" the sinus node);
AV block II and III degree in the absence of an artificial pacemaker (pacemaker);
interstitial lung disease;
dysfunction of the thyroid gland (hypothyroidism, hyperthyroidism);
congenital or acquired lengthening of the QT interval;
combination with drugs capable of prolonging the QT interval and causing the development of paroxysmal tachycardia, including ventricular tachycardia of the "pirouette" type (torsade de pointes): class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, procainamide); class III antiarrhythmics (dofetilide, ibutilide, bretylium tosylate); sotalol; other (non-antiarrhythmic) drugs such as bepridil; vincamine; some antipsychotics phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiapride, veraliprid), butyrophenones (droperidol), sertinoperidol; cisapride; tricyclic antidepressants; antibiotics of the macrolide group (in particular, erythromycin with IV administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine for parenteral administration; diphemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones;
age up to 18 years (efficacy and safety have not been established);
lactose intolerance (lactase deficiency), glucose-galactose malabsorption syndrome (the drug contains lactose);
hypersensitivity to iodine, amiodarone or excipients of the drug.
It caution should be used within decompensated or severe chronic (III-IV functional class according to NYHA classification) heart failure, liver failure, bronchial asthma, severe respiratory failure, in elderly patients (high risk of severe bradycardia), with AV block of I degree ...
Application during pregnancy and lactation
The currently available clinical information is insufficient to determine the possibility or impossibility of the occurrence of malformations in the embryo when using amiodarone in the first trimester of pregnancy.
Since the fetal thyroid gland begins to bind iodine only from the 14th week of pregnancy (amenorrhea), the effect of amiodarone on it is not expected in the case of its earlier use. Excess iodine when using 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.
Due to the effect of the drug on the fetal thyroid gland, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit outweighs the risks (with life-threatening ventricular heart rhythm disturbances).
Amiodarone is excreted in breast milk in significant amounts, therefore it is contraindicated during breastfeeding (during this period, the drug should be canceled or breastfeeding should be stopped).
Application for violations of liver function
Use with caution in liver failure.
Application for impaired renal function
Insignificant excretion of the drug in the urine allows prescribing the drug for renal failure in medium doses. Amiodarone and its metabolites are not dialyzed.
Use in children
Contraindication: children and adolescents under 18 years of age (efficacy and safety have not been established).
Use in elderly patients
Use with caution in elderly patients (high risk of severe bradycardia).
Because. side effects of amiodarone are dose-dependent, patients should be treated with the lowest effective doses to minimize the possibility of their occurrence.
Patients should be advised to avoid exposure to direct sunlight or to take protective measures (eg sunscreen, wearing appropriate clothing) during treatment.
Before starting amiodarone, it is recommended to conduct an ECG study and determine the level of potassium in the blood. Hypokalemia should be corrected before starting amiodarone. During treatment, it is necessary to regularly monitor the ECG (every 3 months) and the activity of transaminases and other indicators of liver function.
In addition, due to the fact that amiodarone can cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, before taking amiodarone, a clinical and laboratory (serum TSH concentration, determined using an ultrasensitive TSH test) should be examined for the subject of detecting dysfunction and diseases of the thyroid gland. During treatment with amiodarone and for several months after its termination, the patient should be regularly examined for clinical or laboratory signs of changes in thyroid function. If thyroid dysfunction is suspected, it is necessary to determine the concentration of TSH in the blood serum (using an ultrasensitive test for TSH).
Increased ventricular defibrillation rates and / or increased thresholds for pacemakers or implanted defibrillators have been reported in patients on long-term treatment for arrhythmias, which may reduce the effectiveness of these devices. Therefore, before starting or during treatment with amiodarone, you should regularly check their correct functioning.
Regardless of the presence or absence of pulmonary symptoms during treatment with amiodarone, it is recommended to conduct an X-ray examination of the lungs and pulmonary function tests every 6 months.
The onset of shortness of breath or dry cough, both isolated and accompanied by a worsening of the general condition (fatigue, weight loss, fever), may indicate pulmonary toxicity, such as interstitial pneumonitis, the suspicion of the development of which requires an X-ray examination of the lungs and pulmonary functional samples.
Because prolongation of repolarization of the ventricles of the heart, the pharmacological effect Kordaronformulation® causes some ECG changes: lengthening QT interval, QTc (korregirovat) may cause waves U. permissible increase QT intervalwith no more than 450 ms or no more than 25% of the original magnitudes. These changes are not a manifestation of the toxic effect of the drug, however, they require monitoring to adjust the dose and assess the possible proarrhythmogenic effect of the drug Cordaron®.
With the development of II and III degree AV block, sinoatrial block or double-bundle intraventricular block, treatment should be discontinued. In the event of grade I AV block, monitoring should be intensified.
Although the occurrence of arrhythmias or the aggravation of existing rhythm disturbances, sometimes fatal, has been noted, the proarrhythmogenic effect of amiodarone is mild (less pronounced than with most antiarrhythmic drugs) and usually manifests itself in the context of factors that increase the duration of the QT interval, such as interactions with other drugs and / or in case of violations of the content of electrolytes in the blood. Despite the ability of amiodarone to increase the duration of the QT interval, it showed low activity in provoking ventricular tachycardia of the "pirouette" type.
If vision is blurry or if visual acuity is reduced, an ophthalmologic examination, including a fundus examination, is urgently needed. With the development of neuropathy or optic neuritis caused by amiodarone, the drug must be discontinued due to the risk of blindness.
Since Cordaron® contains iodine, its intake can disrupt the absorption of radioactive iodine and distort the results of radioisotope studies of the thyroid gland, however, taking the drug does not affect the reliability of determining the content of T3, T4 and TSH in blood plasma. Amiodarone inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and can cause isolated biochemical changes (an 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 the cause to cancel amiodarone.
The development of hypothyroidism can be suspected when the following clinical signs, usually mild, appear: weight gain, cold intolerance, decreased activity, excessive bradycardia.
Before surgery, the anesthesiologist should be informed that the patient is taking Cordaron®.
Prolonged treatment with Kordaron® can enhance hemodynamic risk inherent local or general anesthesia. This applies in particular to its bradycardic and hypotensive effects, decreased cardiac output and conduction disturbances.
In addition, in patients taking Cordaron®, in rare cases, immediately after surgery, acute respiratory distress syndrome was noted. With mechanical ventilation, these patients require careful monitoring.
Recommended careful monitoring of liver function tests (determination of the activity of transaminases) before ingestion Kordaron® and regularly during drug treatment. When taking Cordaron® , acute liver dysfunction (including hepatocellular failure or liver failure, sometimes fatal) and chronic liver damage are possible. Therefore, treatment with amiodarone should be discontinued when the activity of transaminases is 3 times higher than the ULN.
Clinical and laboratory signs of chronic hepatic failure when taking amiodarone inside can be minimally pronounced (hepatomegaly, an increase in transaminase activity, 5 times higher than ULN) and reversible after discontinuation of the drug, however, cases of death have been reported in liver damage.
Effects on the ability to drive vehicles and use mechanisms
Based on safety data, there is no evidence that amiodarone impairs 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 treatment with Cordaron®, it is advisable to refrain from driving and engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.
Symptoms: When very large doses are taken, several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal ventricular tachycardia of the "pirouette" type and liver damage have been described. Perhaps a slowdown in AV conduction, an increase in already existing heart failure.
Treatment: gastric lavage, the use of activated charcoal, if the drug is recently taken, in other cases symptomatic therapy is carried out: with bradycardia - beta-adrenostimulants or installation of a pacemaker, with ventricular tachycardia of the "pirouette" type - intravenous administration of magnesium salts or cardiostimulation.
Neither amiodarone nor its metabolites are removed by hemodialysis. There is no specific antidote.
Drugs that can cause bi-directional pirouette-type ventricular tachycardia or prolong the QT interval
Drugs that can cause pirouette-type ventricular tachycardia
Combination therapy with drugs that can cause pirouette-type ventricular tachycardia is contraindicated because the risk of developing potentially lethal ventricular tachycardia of the "pirouette" type increases. These include:
antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide, procainamide), sotalol, bepridil;
other (non-antiarrhythmic) drugs such as vincamine; some antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, veraliprid), butyrophenones (droperidol), sertinimidol; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with intravenous injection, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine for parenteral administration; diphemanil methyl sulfate; mizolastine; astemizole; terfenadine.
Drugs that can increase the duration of the QT interval
Co-administration of amiodarone with drugs that can increase the duration of the QT interval should be based on a careful assessment for each patient of the ratio of the expected benefit and potential risk (the possibility of an increased risk of developing ventricular tachycardia of the "pirouette" type), when using such combinations it is necessary to constantly monitor the ECG of patients (to detect prolongation of the QT interval), the content of potassium and magnesium in the blood.
Fluoroquinolones, including moxifloxacin, should be avoided in patients taking amiodarone.
Drugs that slow down the heart rate or cause disturbances in automatism or conduction.
Combination therapy with these drugs is not recommended.
Beta-blockers, blockers of slow calcium channels, which reduce heart rate (verapamil, diltiazem), can cause violations of automatism (the development of excessive bradycardia) and conduction.
Drugs that can cause hypokalemia
Not recommended combinations
with laxatives that stimulate intestinal motility, which can cause hypokalemia, which increases the risk of developing ventricular tachycardia of the "pirouette" type. When combined with amiodarone, laxatives of other groups should be used.
Combinations requiring caution when used
with diuretics that cause hypokalemia (in monotherapy or in combination with other drugs);
with systemic corticosteroids (glucocorticoids, mineralocorticoids), tetracosactide;
with amphotericin B (intravenous injection).
It is necessary to prevent the development of hypoglycemia, and in case of its occurrence, restore the potassium level in the blood to normal levels, monitor the concentration of electrolytes in the blood and ECG (for possible prolongation of the QT interval), and in case of ventricular tachycardia of the "pirouette" type, antiarrhythmic drugs should not be used (ventricular pacing should be started; possibly intravenous administration of magnesium salts).
Preparations for inhalation anesthesia The
following severe complications have been reported in patients taking amiodarone during general anesthesia: bradycardia (resistant to the administration of atropine), lowering blood pressure, conduction disturbances, and decreased cardiac output.
There were very rare cases of severe complications from the respiratory system, sometimes fatal (acute respiratory distress syndrome in adults, which developed immediately after surgery, and the occurrence of which is associated with high oxygen concentrations).
Drugs that slows the heart rate (clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine, neostigmine bromide), pilocarpine
risk of excessive bradycardia (cumulative effects).
The effect of amiodarone on other drugs
Amiodarone and / or its metabolite desethylamiodarone inhibit isoenzymes CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein and can increase the systemic exposure of drugs that are their substrates.Due to the prolonged T1/2 of amiodarone, this interaction can be observed even several months after discontinuation its reception.
drugs that are substrates of P-gp
Amiodarone is an inhibitor of P-gp., that its joint reception expected with drugs that are substrates of P-gp, will increase the systemic exposure of the latter.
Cardiac glycosides (preparations of digitalis)
The possibility of automaticity violations (vyra female bradycardia) and atrioventricular conduction. In addition, the combination of digoxin with amiodarone may increase the concentration of digoxin in the blood plasma (due to a decrease in its clearance). Therefore, when combining digoxin with amiodarone, it is necessary to determine the concentration of digoxin in the blood and monitor possible clinical and electrocardiographic manifestations of digitalis intoxication. Reducing digoxin doses may be required.
Caution should be exercised while using amiodarone with dabigatran due to the risk of bleeding. Dosage adjustment of dabigatran may be required according to the directions in its instructions for use.
Drugs that are substrates of the CYP2C9 isoenzyme
Amiodarone increases the concentration in the blood of drugs that are substrates of the CYP2C9 isoenzyme, such as warfarin or phenytoin by inhibiting cytochrome P450 2C9.
When warfarin is combined with amiodarone, the effects of an indirect anticoagulant may increase, which increases the risk of bleeding. The prothrombin time should be monitored more often (by determining MHO) and the dose of the anticoagulant should be adjusted, both during treatment with amiodarone and after stopping it.
When phenytoin is combined with amiodarone, an overdose of phenytoin may develop, which can lead to the appearance of neurological symptoms; clinical monitoring and dose reduction of phenytoin is necessary at the first signs of overdose, it is desirable to determine the concentration of phenytoin in blood plasma.
Medicines that are substrates of the CYP2D6 isoenzyme
Amiodarone increases the plasma concentration of flecainide by inhibiting the CYP2D6 isoenzyme, and therefore requires a dose adjustment of flecainide.
Drugs that are substrates of the CYP3A4 isoenzyme
When amiodarone, an inhibitor of the CYP3A4 isoenzyme, is combined with these drugs, their plasma concentrations may increase, which may lead to an increase in their toxicity and / or an increase in pharmacodynamic effects and may require a decrease in their doses. These medicines are listed below.
The combination of cyclosporine with amiodarone can increase plasma concentrations of cyclosporine, dose adjustment is necessary.
The combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects.
HMG-CoA reductase inhibitors (statins) (simvastatin, atorvastatin and lovastatin)
Increased risk of muscle toxicity of statins when used simultaneously with amiodarone. The use of statins that are not metabolized by the CYP3A4 isoenzyme is recommended.
Other drugs metabolized by the CYP3A4 isoenzyme: lidocaine (risk of developing sinus bradycardia and neurological symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (risk of increased side effects), midazolam (risk of psychomotor effects), triazolam, dihydroergotamine, ergotamine, colchicine.
A drug that is a substrate of CYP2D6 and CYP3A4 isoenzymes - dextromethorphan
Amiodarone inhibits CYP2D6 and CYP3A4 isoenzymes and can theoretically increase the plasma concentration of dextromethorphan.
Clopidogrel is an inactive thienopyrimidine drug that is metabolized in the liver to form active metabolites. There is a 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 and increase its concentration in the blood and, accordingly, its pharmacodynamic and side effects.
It is recommended to avoid taking CYP3A4 inhibitors (for example, grapefruit juice and certain drugs such as cimetidine and HIV protease inhibitors (including indinavir) during amiodarone therapy. HIV protease inhibitors, when used simultaneously with amiodarone, may increase the concentration of amiodarone blood.
Inductors isoenzyme CYP3A4
Rifampicin is a potent inducer isoenzyme CYP3A4, when combined with amiodarone it can reduce the plasma concentration of amiodarone and dezetilamiodarona.
formulations Hypericum perforatum
St. John's wort is a potent inducer isoenzyme CYP3A4. in this regard, it is theoretically possible reduction in plasma concentrations of amiodarone and reduction of its effect (clinical data are not available).
The frequency of side effects has been determined according to the WHO classification: very common (≥10%); often (≥1%, <10); infrequently (≥0.1%, <1%); rarely (≥0.01%, <0.1%); very rarely, including isolated messages (<0.01%); the frequency is unknown (the frequency cannot be determined from the available data).
From the side of the cardiovascular system: often - bradycardia, usually moderate, the severity of which depends on the dose of the drug; infrequently - conduction disturbance (sinoatrial blockade, AV blockade of various degrees), arrhythmogenic action (there are reports of new arrhythmias or worsening of existing ones, in some cases - with subsequent cardiac arrest); Based on the data available it is impossible to determine whether the occurrence of arrhythmias caused by the action of the drug Kordaron®,severity of cardiovascular disease, or is a consequence of treatment failure. These effects are observed mainly in cases of the use of the drug Cordaron® in conjunction with drugs that lengthen the period of repolarization of the ventricles of the heart (QT intervals) or in case of violations of electrolytes in the blood.
Very rarely - severe bradycardia or, in exceptional cases, stopping the sinus node, which were observed in some patients (patients with sinus node dysfunction and elderly patients), vasculitis; frequency unknown - progression of chronic heart failure (with prolonged use), ventricular tachycardia of the "pirouette" type.
On the part of the digestive system: very often - nausea, vomiting, dysgeusia (dullness or loss of taste), usually occurring when the loading dose is taken and passing after its decrease.
From the liver and biliary tract: very often - an isolated increase in the activity of transaminases in the blood serum, usually moderate (exceeding normal values by 1.5-3 times; decreases with dose reduction or spontaneously); often - acute liver damage with increased activity of transaminases and / or jaundice, including the development of liver failure, sometimes fatal; very rarely - chronic liver diseases (pseudo-alcoholic hepatitis, cirrhosis), sometimes fatal. Even with a moderate increase in the activity of transaminases in the blood, observed after treatment lasted for more than 6 months, chronic liver damage should be suspected.
From the respiratory system: often - pulmonary toxicity, sometimes fatal (alveolar / interstitial pneumonitis or fibrosis, pleurisy, bronchiolitis obliterans with pneumonia). Although these changes can lead to the development of pulmonary fibrosis, they are mainly reversible with early withdrawal of amiodarone and with or without GCS. Clinical manifestations usually disappear within 3-4 weeks. Restoration of the radiographic picture and lung function occurs more slowly (several months). The appearance of severe shortness of breath or dry cough in a patient taking amiodarone, both accompanied and not accompanied by a deterioration in the general condition (increased fatigue, weight loss, increased body temperature) requires a chest X-ray and, if necessary, discontinuation of the drug.
Very rarely - bronchospasm (in patients with severe respiratory failure, especially in patients with bronchial asthma), acute respiratory distress syndrome (sometimes fatal and sometimes immediately after surgery; the possibility of interaction with high oxygen concentrations is assumed).
Frequency unknown - pulmonary hemorrhage.
On the part of the organ of vision: very often - microdeposits in the corneal epithelium, consisting of complex lipids, including lipofuscin, they are usually limited to the pupil area and do not require discontinuation of treatment and disappear after discontinuation of the drug, sometimes they can cause visual impairment in the form of a colored halo or blur contours in bright light; very rarely - optic neuritis / optic neuropathy (the connection with amiodarone has not yet been established; however, since optic neuritis can lead to blindness, if blurred vision or decreased visual acuity appears while taking Cordaron®, it is recommended to conduct a complete ophthalmological examination, including fundoscopy, and stop taking the drug if optic neuritis is detected).
From the endocrine system: often - hypothyroidism (weight gain, chilliness, apathy, decreased activity, drowsiness, excessive, compared with the expected effect of amiodarone, bradycardia). The diagnosis is confirmed by the detection of an elevated serum TSH level (using a hypersensitive TSH test); normalization of thyroid function is usually observed within 1-3 months after stopping treatment; in life-threatening situations, treatment with amiodarone can be continued with the simultaneous additional administration of L-thyroxine under the control of serum TSH levels.
Hyperthyroidism, sometimes fatal, also often occurs, the appearance of which is possible during and after treatment (cases of hyperthyroidism that developed several months after the withdrawal of amiodarone have been described). Hyperthyroidism is more secretive, with fewer symptoms: minor unexplained weight loss, decreased antiarrhythmic and / or antianginal efficacy; mental disorders in elderly patients or even the phenomenon of thyrotoxicosis. The diagnosis is confirmed by the detection of a reduced serum TSH level (using a hypersensitive TSH test). If hyperthyroidism is detected, amiodarone should be discontinued. Normalization of thyroid function usually occurs within a few months after drug withdrawal. In this case, the clinical symptoms normalize earlier (after 3-4 weeks) than the normalization of the level of thyroid hormones occurs. Severe cases can be fatal and therefore require urgent medical attention. Treatment in each case is selected individually. If the patient's condition worsens both due to the thyrotoxicosis itself and in connection with a dangerous imbalance between myocardial oxygen demand and its delivery, it is recommended to immediately begin treatment: the use of antithyroid drugs (which may not always be effective in this case), treatment of GCS ( 1 mg / kg), which lasts long enough (3 months), beta-blockers.
Very rarely - syndrome of impaired secretion of ADH.
From the skin and subcutaneous tissues: very often - photosensitization; often (in the case of prolonged use of the drug in high daily doses) - grayish or bluish pigmentation of the skin (after stopping treatment, this pigmentation slowly disappears); very rarely - erythema (during radiation therapy), skin rash (usually not very specific), alopecia, exfoliative dermatitis, alopecia; frequency unknown - urticaria.
From the nervous system: often - tremors or other extrapyramidal symptoms, sleep disturbances, nightmares; infrequently - sensorimotor peripheral neuropathies and / or myopathy (usually reversible within several months after discontinuation of the drug, but sometimes not completely); very rarely - cerebellar ataxia, benign intracranial hypertension (pseudotumor of the brain), headache.
On the part of the genitals and breast: very rarely - epididymitis, impotence.
From the hematopoietic system: very rarely - thrombocytopenia, hemolytic anemia, aplastic anemia.
Allergic reactions: frequency unknown - angioedema (Quincke's edema).
Laboratory and instrumental data: very rarely - an increase in the concentration of creatinine in the blood serum.
General disorders: frequency unknown - formation of granulomas, including bone marrow granulomas.