Instructions for Rotarithmil tablets 200 mg blister No. 30
Composition
active ingredient: amiodarone;
1 tablet contains amiodarone hydrochloride 200 mg;
Excipients: corn starch; lactose monohydrate; povidone (K 90); magnesium stearate; colloidal anhydrous silicon dioxide; pregelatinized starch.
Dosage form
Pills.
Main physicochemical properties: round white tablets with a dividing line.
Pharmacotherapeutic group
Class III antiarrhythmic drugs. ATX code C01B D01.
Pharmacological properties
Pharmacodynamics.
The active ingredient of the drug, amiodarone, belongs to the main representatives of class III antiarrhythmic drugs (class of repolarization inhibitors).
Antiarrhythmic properties of amiodarone.
Prolongation of phase 3 of the myocardial action potential, mainly due to inhibition of potassium channels (class III according to the Vaughan–Williams classification).
Slowing of the heart rate due to inhibition of sinus node automaticity. This effect is not blocked by atropine.
Non-competitive alpha- and beta-adrenergic action.
Slowing of sinoatrial, atrial, and nodal conduction, which becomes more pronounced with increasing heart rate.
No changes in intraventricular conduction.
Increased refractory period and decreased myocardial excitability at the atrial, nodal, and ventricular levels.
Slowing of conduction and prolongation of refractory periods in accessory atrioventricular conduction pathways.
Other properties of amiodarone.
Reduced oxygen consumption due to a moderate decrease in peripheral vascular resistance and a decrease in heart rate.
Increased coronary blood flow due to a direct effect on myocardial vascular smooth muscle and maintenance of cardiac output against the background of reduced blood pressure and peripheral vascular resistance and in the absence of negative inotropic effects.
A meta-analysis of data from 13 prospective, randomized, controlled trials was performed, involving 6553 patients with recent myocardial infarction (78%) or chronic heart failure (22%).
The average duration of follow-up of patients ranged from 0.4 to 2.5 years. The average daily maintenance dose of the drug varied from 200 to 400 mg.
This meta-analysis demonstrated that amiodarone statistically significantly reduced overall mortality by 13% (95% CI: 0.78-0.99; p = 0.030) and arrhythmia-related mortality by 29% (95% CI: 0.59-0.85; p = 0.0003).
However, these results should be interpreted with caution due to the heterogeneity of different studies (differences are mainly related to the populations included in the studies, the duration of the patient follow-up period, the methodology used and the results of the studies).
The percentage of patients who underwent drug withdrawal was higher in the amiodarone group (41%) than in the placebo group (27%).
Seven percent of patients taking amiodarone developed hypothyroidism, compared with 1% in the placebo group. Hyperthyroidism was diagnosed in 1.4% of patients in the amiodarone group, compared with 0.5% in the placebo group.
Interstitial pneumopathy developed in 1.6% of patients in the amiodarone group compared with 0.5% in the placebo group.
Pediatric population.
No controlled clinical trials have been conducted in children. According to the literature, the safety of amiodarone has been studied in 1118 children with various types of arrhythmias.
The following dosages of the drug were used in clinical studies among children:
loading dose: 10-20 mg/kg/day for 7-10 days (i.e. 500 mg/m2/day based on body surface area);
maintenance dose: the minimum effective dose; based on individual response, it may range from 5 to 10 mg/kg/day (i.e. 250 mg/m2/day based on body surface area).
Pharmacokinetics.
Amiodarone is a compound characterized by slow transport and high tissue affinity.
Its oral bioavailability, depending on the individual characteristics of the patient, can be from 30% to 80% (on average - 50%). After a single dose of the drug, maximum plasma concentrations are reached within 3-7 hours.
Therapeutic activity is manifested on average within one week of taking amiodarone (from several days to two weeks).
The elimination half-life of amiodarone is long and has considerable interindividual variability (20 to 100 days). During the first days of treatment, the drug accumulates in most body tissues, especially adipose tissue. Elimination begins after a few days, and the drug intake/excretion ratio reaches equilibrium within one or more months, depending on the patient.
Such characteristics justify the use of loading doses to quickly achieve the level of drug uptake by tissues necessary for the manifestation of its therapeutic activity.
Since only a small amount of the drug is eliminated in the urine, normal doses can be used in patients with renal insufficiency.
After discontinuation of the drug, its elimination continues for several months. It should be noted that residual activity of the drug may be detected for a period of time from 10 days to 1 month.
Amiodarone is primarily metabolized by cytochrome CYP4503A4, but also by cytochrome CYP2C8. Amiodarone and its metabolite, desethylamiodarone, are potent inhibitors of cytochromes CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6, and CYP2C8 in vitro. Amiodarone and desethylamiodarone may also inhibit the function of transport proteins such as P-glycoprotein and organic cation transporter type 2 (OCT2). One study reported a 1.1% increase in creatinine (OCT2 substrate).
In vivo data suggest an interaction between amiodarone and substrates of CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein.
Pediatric population.
No controlled clinical studies have been conducted in children. The limited data available do not indicate any differences in pharmacokinetic parameters between adults and children.
Preclinical data.
Results of a 2-year carcinogenicity study in animals showed that amiodarone led to an increase in the number of follicular thyroid tumors (adenomas and/or carcinomas) in animals of both sexes at clinically relevant exposures.
Since the results of the mutagenicity study were negative, the development of this type of tumor is explained more by an epigenetic rather than a genotoxic mechanism.
Animal studies have not shown any carcinomas, but dose-dependent follicular hyperplasia of the thyroid gland was observed. These effects on the thyroid gland in animals may have been due to the effect of amiodarone on the synthesis and/or release of thyroid hormones. These data have little relevance to human use.
Indication
Prevention of relapses:
ventricular tachycardia, which poses a threat to the patient's life (treatment should 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 agents do not show a 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
Known hypersensitivity to iodine, amiodarone or other components of the drug.
Sinus bradycardia, sinoatrial heart block, except in cases of an implanted pacemaker.
Sick sinus syndrome (risk of sinus arrest), except in cases of implanted pacemaker.
Severe atrioventricular conduction disorders, except in cases of an implanted pacemaker.
Hyperthyroidism.
Concomitant use with drugs capable of causing paroxysmal ventricular tachycardia of the torsades de pointes type (except antiparasitic drugs, neuroleptics and methadone):
class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide);
class III antiarrhythmics (sotalol, dofetilide, ibutilide);
other medicines such as arsenic compounds, bepridil, cisapride, citalopram, escitalopram, diphemanil, dolasetron IV, domperidone, dronedarone, erythromycin IV, levofloxacin, mechitazine, mizolastine, vincamine IV, moxifloxacin, prucalopride, spiramycin IV, toremifene, vincamine IV (see section "Interaction with other medicines and other types of interactions").
Concomitant use with telaprevir, cobicistat.
II and III trimesters of pregnancy.
Breastfeeding period.
Interaction with other medicinal products and other types of interactions
Antiarrhythmic drugs.
Many antiarrhythmic drugs inhibit cardiac automaticity, conduction, and myocardial contractility.
Concomitant use of antiarrhythmics from different classes may be beneficial, but treatment with such a combination usually requires close clinical and ECG monitoring. Concomitant use of antiarrhythmics that may induce torsades de pointes (such as amiodarone, disopyramide, quinidine compounds, sotalol, and others) is contraindicated.
The simultaneous use of antiarrhythmic drugs of the same class is not recommended, except in exceptional cases, as such treatment increases the risk of cardiac side effects.
Concomitant use of amiodarone with drugs that have a negative inotropic effect, promote bradycardia and/or slow atrioventricular conduction, therefore requires careful clinical and ECG monitoring.
This serious arrhythmia can be induced by certain drugs, whether or not they are antiarrhythmics. Predisposing factors include hypokalemia (see section "Potassium-lowering drugs"), bradycardia (see section "Heart rate-slowing drugs"), or congenital or acquired pre-existing QT prolongation.
Drugs that may induce torsades de pointes include, in particular, class Ia and III antiarrhythmics and some neuroleptics. For dolasetron, erythromycin, spiramycin and vincamine, this interaction occurs only when the dosage forms for intravenous administration are used.
The simultaneous use of two drugs, each of which is a drug that contributes to the occurrence of torsades de pointes, is usually contraindicated.
However, methadone, antiparasitic drugs (halofantrine, lumefantrine, pentamidine), and neuroleptics, the use of which is considered absolutely necessary, are not contraindicated, but are not recommended for use simultaneously with other drugs that contribute to the occurrence of torsades de pointes.
Drugs that slow the heart rate.
Many drugs can cause bradycardia, including class Ia antiarrhythmics, beta-blockers, some class III antiarrhythmics, some calcium channel blockers, digitalis, pilocarpine, and anticholinesterase drugs.
Effects of amiodarone on other drugs.
Amiodarone and/or its metabolite, desethylamiodarone, inhibit CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein and may increase exposure to their substrates. Given the long duration of action of amiodarone, such interactions may persist for several months after discontinuation of amiodarone treatment.
Effects of other drugs on amiodarone.
CYP3A4 and CYP2C8 inhibitors have the potential to inhibit the metabolism of amiodarone and thus increase its exposure.
CYP3A4 inhibitors (e.g. grapefruit juice and some medications) are generally not used during treatment with amiodarone.
Contraindicated combinations (see section "Contraindications").
Medicinal products that may induce torsades de pointes (except antiparasitics, neuroleptics and methadone; see section “Not recommended combinations”):
class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide);
class III antiarrhythmics (dofetilide, ibutilide, sotalol);
other medications (arsenic compounds, bepridil, cisapride, citalopram, escitalopram, diphemanil, dolasetron IV, domperidone, dronedarone, erythromycin IV, levofloxacin, mechitazine, mizolastine, vincamine IV, moxifloxacin, prucalopride, spiramycin IV, toremifene).
Increased risk of developing ventricular arrhythmias, especially torsades de pointes.
Telaprevir: Cardiomyocyte automatism and conduction disorders with risk of excessive bradycardia
Cobicistat: There is a risk of increased incidence of amiodarone-induced side effects due to decreased metabolism.
Combinations are not recommended (see section "Special instructions for use").
Sofosbuvir: Concomitant use of amiodarone with medicinal products containing sofosbuvir may cause severe symptomatic bradycardia. Should only be used if no alternative treatment is available. Close monitoring is recommended when these medicinal products are used concomitantly (see section 4.4).
CYP3A4 substrates: Amiodarone is an inhibitor of CYP3A4 and increases plasma concentrations of CYP3A4 substrates, leading to a potential increase in the toxicity of these substrates.
Cyclosporine: Increased plasma concentrations of cyclosporine due to reduced hepatic metabolism, with the risk of nephrotoxic effects.
During treatment with amiodarone, quantitative determination of cyclosporine plasma concentrations, monitoring of renal function, and adjustment of cyclosporine dose should be performed.
Diltiazem for injection. Risk of bradycardia and atrioventricular block.
If the use of this combination cannot be avoided, close clinical supervision and continuous ECG monitoring should be performed.
Fingolimod. Potentiation of bradycardia-induced effects, possibly fatal. This is especially true for beta-blockers that inhibit adrenergic compensation mechanisms. Clinical supervision and continuous ECG monitoring should be carried out for 24 hours after the first dose of the drug.
Verapamil for injection. Risk of bradycardia and atrioventricular block.
If the use of this combination cannot be avoided, close clinical supervision and continuous ECG monitoring are necessary.
Neuroleptics that can induce paroxysmal ventricular tachycardia of the torsades de pointes type (amisulpride, chlorpromazine, cyamemazine, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperon, pipotiazine, sertindole, sulpiride, sultopride, tiapride, zuclopenthixol). Increased risk of ventricular arrhythmias, especially torsades de pointes.
Methadone: Increased risk of ventricular arrhythmias, especially torsades de pointes.
Fluoroquinolones, except levofloxacin and moxifloxacin (contraindicated combinations). Increased risk of ventricular arrhythmias, especially torsades de pointes.
Stimulant laxatives. Increased risk of ventricular arrhythmias, especially torsades de pointes ventricular tachycardia (hypokalemia is a precipitating factor). Any hypokalemia should be corrected before use and ECG monitoring and clinical surveillance should be performed, along with electrolyte monitoring.
Fidaxomicin: Increased plasma concentrations of fidaxomicin.
Combinations requiring precautions for use.
P-glycoprotein substrates: Amiodarone is an inhibitor of P-glycoprotein. Co-administration with P-glycoprotein substrates is expected to increase their plasma concentrations.
Digitalis preparations. Inhibition of automaticity (excessive bradycardia) and disturbances of atrioventricular conduction.
When using digoxin, an increase in blood digoxin levels is observed due to a decrease in digoxin clearance, which requires ECG and clinical monitoring. If necessary, the level of digoxin in the blood plasma should be monitored and its dose adjusted.
Dabigatran: Increased plasma concentrations of dabigatran with increased risk of haemorrhagic events. If dabigatran is used after surgery, clinical monitoring and dose adjustment of dabigatran should be performed as necessary, but not higher than 150 mg/day.
Since amiodarone has a long half-life, interactions may occur for several months after discontinuation of amiodarone treatment.
CYP 2C9 Substrates: Amiodarone increases the concentrations of substances that are CYP 2C9 substrates, such as vitamin K antagonists or phenytoin, by inhibiting cytochrome P450 2C9 enzymes.
Vitamin K antagonists. Potentiation of the effects of vitamin K antagonists and increased risk of bleeding. Monitoring of the international normalized ratio (INR) should be performed more frequently. The dose of the vitamin K antagonist should be adjusted during treatment with amiodarone and for 8 days after the end of treatment.
Phenytoin (by extrapolation also fosphenytoin). Increased plasma concentrations of phenytoin with signs of overdose, especially neurological signs (inhibition of phenytoin metabolism in the liver). Clinical monitoring, monitoring of phenytoin plasma concentrations and, if necessary, adjustment of the phenytoin dose should be carried out.
CYP2D6 substrates:
Flecainide: Amiodarone increases plasma concentrations of flecainide by inhibiting cytochrome CYP2D6. Therefore, flecainide dose adjustment should be considered.
CYP3A4 substrates. Amiodarone is an inhibitor of CYP3A4 and increases the plasma concentration of substrates of this cytochrome, as a result - increases the toxic effects of these substrates.
Statins (simvastatin, atorvastatin, lovastatin). Concomitant use of amiodarone and statins metabolized by CYP3A4, such as simvastatin, atorvastatin, and lovastatin, increases the risk of muscle toxicity (e.g., rhabdomyolysis). When used concomitantly with amiodarone, statins not metabolized by CYP3A4 are recommended.
Other drugs metabolized by CYP3A4 (lidocaine, sirolimus, tacrolimus, sildenafil, midazolam, dihydroergotamine, ergotamine, colchicine, triazolam). Amiodarone is an inhibitor of CYP3A4 and increases the plasma concentrations of these molecules, leading to a potential increase in their toxicity.
Lidocaine. Risk of increased plasma concentrations of lidocaine, which may lead to neurological and cardiac side effects due to inhibition of hepatic metabolism by amiodarone. Clinical and ECG monitoring should be performed, as well as, if necessary, quantitative determination of plasma concentrations of lidocaine. If necessary, adjustment of the lidocaine dose during treatment with amiodarone and after its withdrawal.
Tacrolimus: Increased plasma concentrations of tacrolimus due to inhibition of its metabolism by amiodarone. Quantitative determination of tacrolimus plasma concentrations, monitoring of renal function, and adjustment of tacrolimus dose should be performed when co-administered with amiodarone and after discontinuation of the latter.
Beta-blockers, except sotalol (contraindicated combination) and esmolol (combination requiring precautions for use). Disturbances of automaticity and conduction (suppression of compensatory sympathetic mechanisms). Clinical and ECG monitoring recommended.
Esmolol. Impaired contractility, automatism and conduction (suppression of compensatory sympathetic mechanisms). Clinical and ECG monitoring recommended.
Oral diltiazem. Risk of bradycardia or AV block, especially in elderly patients. Clinical and ECG monitoring recommended.
Oral verapamil. Risk of bradycardia and AV block, especially in elderly patients. Clinical and ECG monitoring recommended.
Some macrolides (azithromycin, clarithromycin, roxithromycin). Increased risk of ventricular arrhythmias, especially torsades de pointes. Clinical and ECG monitoring is recommended during concomitant use of these drugs.
Potassium-depleting drugs: potassium-depleting diuretics (alone or in combination), stimulant laxatives, amphotericin B (when administered intravenously), glucocorticoids (when administered systemically), tetracosactide.
Increased risk of ventricular arrhythmias, especially torsades de pointes (hypokalemia is a predisposing factor). Hypokalemia should be corrected before prescribing the drug and ECG, electrolytes and clinical monitoring should be performed.
Heart rate lowering agents. Increased risk of ventricular arrhythmias, especially torsades de pointes. Clinical and ECG monitoring recommended.
Orlistat: Risk of decreased plasma concentrations of amiodarone and its active metabolite. Clinical monitoring and, if necessary, ECG monitoring is recommended.
Tamsulosin: Risk of increased adverse effects of tamsulosin due to inhibition of its metabolism in the liver. Clinical monitoring should be performed and, if necessary, tamsulosin dose adjustment should be made during treatment with an enzyme inhibitor and after its discontinuation.
Voriconazole: Increased risk of ventricular arrhythmias, especially torsades de pointes, as amiodarone metabolism may be reduced. Clinical and ECG monitoring is required and amiodarone dose adjustment may be necessary.
Combinations that require special attention.
Pilocarpine: Risk of excessive bradycardia (additive effects of drugs that slow the heart rate).
Application features
Heart effects.
Amiodarone induces ECG changes. These changes include prolongation of the QT interval due to prolonged repolarization with possible appearance of a U wave. This is a sign of the therapeutic effect of the drug, not its toxicity.
In elderly patients, amiodarone may cause an increase in heart rate deceleration.
Cases of new arrhythmias or worsening of existing arrhythmias have been reported (see section 4.8). This proarrhythmic effect may be particularly likely in the presence of factors that contribute to QT prolongation, including certain drug combinations and hypokalemia (see sections 4.8 and 4.5).
The risk of drug-induced torsades de pointes with amiodarone is considered lower than with other antiarrhythmic drugs in patients with the same degree of QT prolongation.
An ECG should be performed before using the drug.
In case of development of AV-block II or III degree, sinoatrial block or bifascicular block, the drug should be discontinued. The development of AV-block I degree requires increased patient monitoring.
Thyroid disorders.
Amiodarone may cause thyroid dysfunction, especially in patients with a history of thyroid dysfunction.
It is recommended to perform quantitative determination of thyroid-stimulating hormone (TSH) levels before using the drug, then regularly during treatment and for several months after drug withdrawal, as well as in case of clinical suspicion of thyroid dysfunction (see section "Adverse reactions").
The drug contains iodine, which affects the results of some thyroid function tests (radioactive iodine uptake, protein-bound iodine levels). However, thyroid function tests T3, T4, and high-sensitivity TSH assays remain interpretable.
Lung disorders.
The appearance of dyspnea or non-productive cough, either isolated or associated with deterioration in general condition, should be considered as a possible sign of pulmonary toxicity of amiodarone, for example the development of interstitial pneumonitis, and requires a radiological examination of the patient (see section "Adverse reactions").
Liver disorders.
Regular monitoring of liver function is recommended at the beginning of the drug and periodically during treatment with amiodarone (see section "Adverse reactions").
Neuromuscular disorders.
Amiodarone may cause peripheral sensory-motor or mixed neuropathy and myopathy (see section "Adverse reactions").
If visual acuity or visual acuity deteriorates during treatment, a complete ophthalmological examination, including ophthalmoscopy, should be performed immediately. If optic neuropathy or neuritis caused by amiodarone develops, the drug should be discontinued, as continued treatment may lead to progression of the disorder to blindness ("Adverse Reactions").
Severe skin reactions.
Life-threatening or even fatal skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, may occur with amiodarone. If symptoms suggestive of these conditions develop (e.g. progressive blistering skin rash or mucosal lesions), the drug should be discontinued immediately.
Disorders associated with interaction with sofosbuvir (risk of severe bradycardia)
Severe, potentially life-threatening bradycardia and severe cardiac conduction abnormalities have been reported in patients taking amiodarone in combination with sofosbuvir alone or in combination with other direct-acting antivirals for the treatment of hepatitis C, such as daclatasvir, simeprevir or ledipasvir. Bradycardia usually occurred within hours to days, but symptoms have been reported to occur more frequently, usually within 2 weeks of starting antiviral treatment for hepatitis C (HCV).
Patients treated with sofosbuvir-containing drugs should only take amiodarone if they are intolerant to or have contraindications to other antiarrhythmic agents.
If concomitant use of amiodarone with these drugs is necessary, patients are recommended to have inpatient cardiac monitoring for the first 48 hours of concomitant use of these drugs, followed by outpatient monitoring or daily self-monitoring of heart rate for at least the first 2 weeks of treatment.
Due to the long half-life of amiodarone, appropriate monitoring should also be performed in patients who have stopped taking amiodarone within several months before starting treatment with sofosbuvir alone or in combination with other direct-acting antivirals.
Patients receiving these drugs for the treatment of hepatitis C in combination with amiodarone, regardless of the intake of other drugs that reduce heart rate, should be warned about the symptoms that occur with bradycardia and severe cardiac conduction disorders, and should be informed that in case of their occurrence, it is necessary to seek emergency medical attention.
Disorders associated with interactions with other drugs.
Concomitant use of the drug should only be considered for the prevention of life-threatening ventricular arrhythmias with the following drugs:
beta-blockers, except sotalol (a contraindicated combination) and esmolol (a combination that requires precautions when used), verapamil and diltiazem.
Concomitant use of the drug is not recommended with the following drugs: cyclosporine, diltiazem (for injection) or verapamil (for injection), some antiparasitic drugs (halofantrine, lumefantrine and pentamidine), some neuroleptics (amisulpride, chlorpromazine, cyamemazine, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperon, pipotiazine, sertindole, sulpiride, sultopride, tiapride, zuclopenthixol), fluoroquinolones (except levofloxacin and moxifloxacin), stimulant laxatives, methadone or fingolimod (see section "Interaction with other drugs and other types of interactions").
Electrolyte disturbances.
It is important to consider any situation in which the patient may be at risk of hypokalemia, as hypokalemia may provoke proarrhythmic effects. Hypokalemia must be corrected before starting the drug.
Use during anesthesia.
The anesthesiologist should be informed before surgery that the patient is taking amiodarone.
The side effects of chronic amiodarone treatment may be exacerbated by the hemodynamic risks associated with general or local anesthesia. These effects include, in particular, bradycardia, hypotension, decreased cardiac output, and cardiac conduction disturbances.
In addition, some cases of acute respiratory distress syndrome have been observed in the early postoperative period in patients receiving amiodarone. Therefore, careful monitoring of the condition of such patients during mechanical ventilation is recommended (see section "Adverse reactions").
Transplantation.
In retrospective studies in transplant recipients, the use of amiodarone before heart transplantation was associated with an increased risk of primary graft dysfunction (PGD).
Consideration should be given to prescribing an alternative antiarrhythmic drug as early as possible before transplantation in patients awaiting cardiac transplantation.
Excipient-related disorders.
The drug contains lactose, so it should not be used in patients with galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases).
The undesirable effects listed below are most often associated with excessive use of the drug; they can be avoided or minimized by careful adherence to the minimum maintenance dose.
During treatment with the drug, patients are advised to avoid sunlight or take protective measures against sunlight. The safety and efficacy of amiodarone in children have not been evaluated in controlled clinical trials. Because of the possible increase in the defibrillation threshold and/or the pacing threshold in patients with implanted cardiac defibrillators or pacemakers, this threshold should be checked before using amiodarone and several times after starting its use, as well as each time the dose of the drug is adjusted.
Use during pregnancy or breastfeeding
Pregnancy.
Amiodarone has not shown any teratogenic effects in animal studies, so no malformative effects are expected in humans. To date, substances that cause malformations in humans have been shown to be teratogenic in animals in well-conducted studies in two species.
There are insufficient clinical data to assess the possible teratogenic or fetotoxic effects of amiodarone when used in therapeutic doses during the first trimester of pregnancy.
Since the fetal thyroid gland begins to bind iodine from the 14th week, no effect on the embryonic thyroid gland is expected if amiodarone is administered before this time.
Excessive iodine intake from amiodarone use can lead to fetal hypothyroidism or even the development of a clinical picture of fetal hypothyroidism (development of goiter).
Given the effect of amiodarone on the fetal thyroid gland, the drug is contraindicated from the second trimester of pregnancy.
Breastfeeding period.
Amiodarone and its metabolites, together with iodine, are excreted in breast milk in amounts greater than those present in maternal plasma. Given the risk of hypothyroidism in the infant, breastfeeding is contraindicated during treatment with the drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
When using the drug, the possibility of developing adverse reactions from the nervous system and organs of vision should be taken into account.
Method of administration and doses
The drug is intended for oral use.
The drug should be used only as prescribed by a doctor.
The tablets should be taken orally before meals and washed down with sufficient water.
Adults.
Initial treatment.
The usual recommended dose of the drug is 200 mg (1 tablet) 3 times a day for 8-10 days.
In some cases, higher doses (4-5 tablets per day) are used for initial treatment, but always for a short period of time and under ECG monitoring.
Supportive treatment.
The drug should be used in the minimum effective dose. Depending on the patient's response to the drug, the maintenance dose for adults may range from ½ tablet per day (1 tablet every 2 days) to 2 tablets per day.
Children.
The safety and efficacy of amiodarone in children have not been established, therefore the use of the drug in this category of patients is not recommended.
Overdose
Symptoms.
Cases of acute overdose of amiodarone when administered orally are not well documented.
