Pharmacological properties
Pharmacodynamics. Class III antiarrhythmic agent. The antiarrhythmic effect is due to an increase in the III 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 automatism 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 α- and β-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 OPSS. 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 deposits, liver, spleen, lungs. After a few days, amiodarone is excreted 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. T ½ is 20-100 per day. After cessation of treatment with amiodarone, its excretion from the body occurs within several months. Amiodarone contains iodine, therefore, 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 effect lasts for several days or even weeks.
Indication
tablets:
tachyarrhythmia associated with WPW syndrome; ventricular flutter and fibrillation when other medications cannot be used; all types of paroxysmal tachycardia, including supraventricular, nodal and ventricular tachycardia, atrial fibrillation, when other medications cannot be prescribed.
The tablet form of the drug is used only for the treatment of severe rhythm disturbances that are life-threatening and resistant to other medications, as well as if other drugs are contraindicated.
Treatment should be initiated and monitored only in a hospital setting or under the supervision of a specialist.
Solution for injection
Severe heart rhythm disturbances when treatment with oral amiodarone is inappropriate, in diseases such as:
atrial arrhythmia with high ventricular rate; tachycardia associated with WPW syndrome; documented symptomatic ventricular arrhythmias that result in disability; cardiopulmonary resuscitation for cardiac arrest due to ventricular fibrillation that is resistant to external electrical impulse therapy.
Application
pills
adults
saturation dose
Treatment usually begins with 200 mg (1 tablet) 3 times a day for a week, reducing the dose to 200 mg 2 times a day for the next week.
maintenance dose
The minimum effective dose should be used, depending on the patient's response to the drug. After a period of saturation, the dose can be reduced to 200 or 100 mg/day. Rarely, the patient may require a higher maintenance dose. The maintenance dose should be reviewed regularly, especially if it exceeds 200 mg/day. Excessively high doses during maintenance therapy may cause side effects that are associated with high levels of amiodarone and its metabolites in the body's tissues.
Since Aritmil has a very long T ½, it can be taken every other day (200 mg of the drug can be taken every other day, and 100 mg is recommended to be taken daily). You can take breaks in taking the drug - 2 days a week. The regimen of taking the drug is determined 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.
Solution for injection
For intravenous administration, the dose and frequency of administration are set individually depending on the condition and needs of each patient. Aritmil can be administered only by dissolving it in a 5% glucose solution. Do not dilute with 0.9% sodium chloride solution, as precipitation may occur! Based on the pharmaceutical properties of the drug, the concentration of the solution should not be lower than 600 mg/l, i.e. 2 ampoules of the drug should be diluted in at least 500 ml of 5% glucose solution.
IV infusion: loading dose is 5-7 mg/kg body weight, diluted in 250 ml of 5% glucose solution and administered over 20 min - 2 h. The administration can be repeated 2-3 times within 24 h. The daily dose should not exceed 1200 mg/day. The therapeutic effect of the drug is manifested in the first minutes of administration and disappears gradually, which requires correction of the infusion rate according to the results of treatment and maintenance infusion.
Maintenance dose: 10-20 mg/kg/day (average - 600-800 mg/day to 1200 mg/day) in 250 ml of 5% glucose solution for several days. Infusion therapy usually lasts 4-5 days, can be continuous or intermittent (2-3 times a day). From the 1st day of infusion, it is necessary to begin a gradual transition to oral administration of the drug in a dose of 600-800 to 1200 mg/day.
Intravenous administration of amiodarone in the form of injections is possible only in emergency situations when there are no other therapeutic options, and only in cardiac intensive care units with constant ECG monitoring.
Intravenous injection: the usual dose is 5 mg/kg body weight, diluted in 20 ml of 5% glucose solution and administered over at least 3 minutes. Repeated intravenous injection should not be administered earlier than 15 minutes after the first administration, even if only part of the contents of one ampoule has been used (irreversible collapse is possible).
Do not mix with other drugs in the same syringe!
Children over 3 years of age are given Aritmil to stop arrhythmias in emergency situations according to the following scheme:
The recommended loading dose is 5 mg/kg administered over 20 min to 2 h; the maintenance dose is 10-15 mg/kg/day administered over several hours to several days. If necessary, oral administration of the drug can be started immediately.
Contraindication
Tablets and solution for injection: hypersensitivity to iodine and/or amiodarone or other components of the drug, sinus bradycardia, sinoatrial block, except in patients with an artificial pacemaker (risk of sinus node arrest); high degree of AV block, severe intraventricular conduction disorders (blockade of the 2nd and 3rd bundle branches of the bundle of Hissen), sick sinus syndrome in the absence of an artificial pacemaker; simultaneous use with drugs that can cause polymorphic ventricular tachycardia of the "torsade de pointes" type; thyroid gland dysfunction (hypothyroidism, hyperthyroidism). Before starting treatment, it is necessary to check the thyroid gland function in all patients; pregnancy and breastfeeding.
Solution for injection:
Circulatory collapse or severe arterial hypotension, cardiomyopathy, decompensated heart failure, severe respiratory failure are contraindications for the administration of Aritmil in the form of an intravenous bolus injection (a sharp deterioration of the patient's condition is possible); children under 3 years of age.
The above contraindications are not taken into account when performing cardiopulmonary resuscitation in cases of an attack of resistant ventricular fibrillation.
Side effects
Side effects, information about which is provided below, are classified by organs and systems, the frequency of their occurrence: very common (≥10%); common (≥1% and 10%); uncommon (≥0.1% and 1%); rare (≥0.01% and 0.1%); very rare (0.01%).
Blood and lymphatic system disorders
Tablets: very rarely - hemolytic anemia, aplastic anemia, thrombocytopenia.
Tablets and solution for injection: Cases of bone marrow granulomas have been observed in patients taking amiodarone. The clinical significance of this is unknown.
Cardiovascular system
Tablets and solution for injection: often - bradycardia, usually moderate and dose-dependent;
very rare: marked bradycardia and, in exceptional cases, sinus arrest, the treatment of which differs, especially in the elderly and/or in patients with sinus node dysfunction.
Tablets: infrequently - development or intensification of arrhythmia, sometimes up to cardiac arrest; conduction disorders (sinoatrial blockade, AV blockade of varying degrees). Mainly, these adverse reactions can occur with simultaneous use with drugs that prolong the period of repolarization of the ventricles of the heart or with electrolyte balance disorders.
Solution for injection: very rarely - development or worsening of arrhythmia, sometimes up to cardiac arrest, mainly when used simultaneously with drugs that prolong the period of repolarization of the ventricles of the heart or in case of electrolyte imbalance.
endocrine disorders
Tablets: often - hypothyroidism, hyperthyroidism, sometimes fatal;
very rare: syndrome of inappropriate antidiuretic hormone secretion (SIADH).
ophthalmological disorders
Tablets: very common: microdeposits in the corneal epithelium, usually in the subpupillary area, which are usually only visible during slit-lamp examination and are manifested by 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;
very rare: neuropathy/optic neuritis which may lead to blindness.
Gastrointestinal disorders
Tablets: very common: benign gastrointestinal disorders (nausea, vomiting, dysgeusia), which usually occur during the period of drug saturation and disappear when the dose is reduced.
Solution for injection: very rare: nausea.
Tablets: very common: 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 of the drug or even spontaneously;
often: acute liver function disorders (including liver failure), sometimes fatal, with high serum transaminase levels and/or jaundice. If transaminase levels are significantly elevated, therapy should be discontinued. Periodic monitoring of liver function is recommended during treatment with amiodarone;
very rare: chronic liver diseases (pseudoalcoholic hepatitis, cirrhosis), sometimes fatal.
Solution for injection: very rare: increased 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 failure, sometimes fatal (more often occurs in the first 24 hours of i / v administration of amiodarone), with high serum transaminase levels and / or jaundice. If the level of transaminases increases significantly, therapy should be discontinued. During treatment with amiodarone, periodic monitoring of liver function is recommended.
On the part of the immune system
Tablets: angioedema (there have been a few reports, exact frequency unknown).
Solution for injection: very rare: anaphylactic shock; angioedema (there have been a few reports, exact frequency unknown).
From the nervous system
Tablets: often: extrapyramidal tremor (the appearance of which may dictate dose reduction or drug withdrawal), disturbing dreams, sleep disturbances;
infrequently: peripheral sensorimotor neuropathies and/or myopathies, usually resolving after drug withdrawal;
very rare: cerebellar ataxia (regresses after dose reduction or drug withdrawal), benign intracranial hypertension (pseudotumor cerebri), headache, dizziness.
Solution for injection: very rare: benign intracranial hypertension (pseudotumor cerebri), headache.
From the reproductive system
Tablets: very rare: epididymitis, orchitis, impotence.
Respiratory system
Tablets: often: toxic effects on lung tissue, sometimes fatal (hypersensitivity pneumonitis, alveolar/interstitial pneumonitis or fibrosis, pleurisy, bronchiolitis obliterans associated with pneumonia). Pulmonary disorders, mostly reversible with early discontinuation of the drug. Clinical symptoms usually disappear within 3-4 weeks, followed by a slower recovery of the radiographic picture and lung function (over several months). Therefore, the need for discontinuation of amiodarone and the appropriateness of prescribing glucocorticosteroids should be reconsidered in such cases;
Very rare: bronchospasm in patients with severe respiratory failure, especially in patients with bronchial asthma; acute respiratory distress syndrome, sometimes fatal, most often immediately after surgery (possibly after interaction with high doses of oxygen).
Cases of pulmonary hemorrhage have been reported (exact frequency unknown).
Solution for injection: very rare: interstitial pneumonitis: pulmonary disorders, mostly reversible, with early withdrawal of the drug. Clinical symptoms usually disappear within 3-4 weeks, followed by a slower recovery of the radiographic picture and lung function (over several months). Therefore, the need for amiodarone withdrawal and the appropriateness of glucocorticosteroids should be reconsidered in such cases; acute respiratory distress syndrome, sometimes fatal, most often immediately after surgery (possibly after interaction with high doses of oxygen); bronchospasm and / or apnea in patients with severe respiratory failure, especially patients with bronchial asthma.
Skin and subcutaneous tissue disorders
Tablets: very common: photosensitivity;
Common: gray or blue pigmentation of exposed skin, especially the face, in cases of long-term treatment with high doses of the drug; after discontinuation of treatment, this pigmentation slowly disappears (within 10-12 months).
Very rare: erythema during radiotherapy; rash, usually non-specific; exfoliative dermatitis; alopecia; urticaria (frequency unknown).
Solution for injection: very rare: increased sweating.
Vascular disorders
Tablets: very rare: vasculitis.
Side effects of the drug are usually dose-dependent, so care should be taken to determine the minimum effective maintenance dose to prevent or minimize the risk of adverse effects.
Solution for injection: common: decrease in blood pressure, usually moderate and reversible. Cases of severe hypotension or collapse have been reported with overdose or very rapid administration of the drug;
very rare: feeling hot.
local reactions
Solution for injection: common: reactions at the injection site, such as pain, erythema, swelling, necrosis, hemorrhage, infiltration, inflammation, induration, cellulitis, thrombophlebitis, phlebitis, infectious complications, pigmentation changes.
Special instructions
pills
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 manifestations are dose-dependent, therefore, during maintenance therapy, the minimum effective dose should be used.
Before surgery, it is imperative to warn the anesthesiologist that the patient has received/is receiving amiodarone (risk of respiratory distress syndrome).
To prevent undesirable effects, concomitant therapy should be carefully prescribed, taking into account clinically significant interactions with amiodarone.
Features of use. The drug should be used with caution in the elderly, patients taking cardiac glycosides, due to the risk of developing severe bradycardia, severe conduction disturbances with the possible occurrence of idioventricular rhythm, especially when using high doses. If such conditions occur, treatment with Aritmil should be discontinued, beta-adrenomimetics or glucagon can be used, and if necessary, cardiac pacing.
Due to the long T½ of amiodarone, if bradycardia is severe, it is necessary to consider the feasibility 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.
During treatment with amiodarone, ECG changes are possible: prolongation of the Q-T interval (due to prolonged repolarization), appearance of a U wave, 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 simultaneously with drugs that prolong the period of ventricular repolarization or in case of electrolyte imbalance (especially hypokalemia). It is advisable to correct electrolyte imbalance before starting treatment with Aritmil. The occurrence of new arrhythmias or exacerbation of existing arrhythmias, sometimes fatal, has been reported.
Before starting treatment, each patient should have an ECG and determine the level of potassium in the blood plasma. ECG monitoring is recommended throughout the entire treatment with the drug.
Amiodarone may increase the defibrillation threshold and/or 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 functioning of the equipment after initiation of treatment or dose changes.
Amiodarone may cause thyroid dysfunction (hypothyroidism, hyperthyroidism), especially in patients with a history of thyroid dysfunction (including family history), and in elderly patients. Therefore, careful clinical and laboratory monitoring of thyroid function is necessary before and during treatment (every 6 months), as well as for several months after its completion.
If thyroid dysfunction is suspected, serum TSH levels should be measured.
In life-threatening situations, when hypothyroidism occurs, amiodarone treatment may be continued in combination with levothyroxine, the dose of which is adjusted according to thyroid hormone levels. Euthyroidism is usually restored 3 months after discontinuation of amiodarone treatment.
Hyperthyroidism may occur during treatment with amiodarone or several months after its discontinuation. Fatal cases of hyperthyroidism have been reported, so if it occurs, amiodarone should be discontinued. Clinical recovery usually occurs within several months.
In cases of severe thyroid hyperactivity, the use of antithyroid drugs, possibly in combination with corticosteroids, should be considered.
Aritmil contains iodine, so it may affect the results of tests for the accumulation of radioactive iodine in the thyroid gland, but does not affect the levels of T3, T4, and TSH hormones.
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.
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.
Chronic liver disease has been reported with treatment for more than 6 months (pseudoalcoholic hepatitis, cirrhosis). Clinical symptoms and laboratory changes may be minimal (hepatomegaly may occur, transaminase levels may be 1.5-5 times higher than normal). Therefore, regular monitoring of liver function is recommended during treatment. Clinical and laboratory abnormalities usually resolve after discontinuation of the drug, but there have been isolated fatal cases.
It is undesirable to drink alcohol during treatment with Aritmil, although there have been no reports of potentiation of the negative effects on the liver.
Amiodarone can cause peripheral sensorimotor neuropathy and/or myopathy with prolonged use, which usually resolves after discontinuation of the drug. However, recovery may be incomplete, very slow, and may not occur until several months after discontinuation.
The occurrence of dyspnea and unproductive cough may be associated with the manifestation of amiodarone toxicity on the respiratory system (hypersensitivity pneumonitis, alveolar/interstitial pneumonitis or fibrosis, pleurisy, bronchiolitis obliterans with pneumonia).
Patients who develop dyspnea or productive cough, either alone or with worsening general condition (fatigue, weight loss, fever), should have a chest X-ray and, if necessary, discontinue the drug.
Such pneumopathies can lead to pulmonary fibrosis, but they are generally reversible with early withdrawal of amiodarone, with or without corticosteroids. Clinical symptoms usually resolve within 3 to 4 weeks, followed by a slower recovery of radiographic and pulmonary function (over several months).
In some cases, pleurisy associated with interstitial pneumonia may develop.
In patients with severe respiratory disorders and especially in patients with asthma, bronchospasm may occur in isolated cases.
In some cases, patients receiving amiodarone have experienced acute distress syndrome immediately after surgery (possibly incompatibility with high oxygen concentrations). Careful monitoring of such patients is recommended when using mechanical ventilation.
It is not recommended to use Aritmil with beta-blockers (except sotalol and esmolol), some calcium channel blockers (verapamil, injectable form of diltiazem), laxatives that stimulate intestinal motility and can cause hypokalemia. Also, with simultaneous use of Aritmil and flecainide, it is necessary, given the increase in plasma levels of the latter, 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 due to the risk of increasing the concentration of amiodarone in the blood.
Use during pregnancy and breastfeeding. Since the drug acts on the fetal thyroid gland, use of the drug during pregnancy is contraindicated, except in special situations.
Amiodarone is excreted in breast milk in significant quantities, therefore, if it is necessary to take the drug by breastfeeding women, breastfeeding should be discontinued during treatment.
Children: Controlled clinical trials to study the safety and efficacy of the drug in the treatment of children have not been conducted.
Ability to influence the reaction rate when driving vehicles or operating other mechanisms. The drug may adversely affect the reaction rate when driving vehicles or operating other mechanisms, especially in patients with amiodarone-induced visual disorders.
Solution for injection
Special precautions. Aritmil for intravenous administration is intended for use only in specialized hospital departments with constant monitoring of the patient's condition (ECG, blood pressure) in cases where rapid achievement of an antiarrhythmic effect is necessary or when oral administration is impossible.
Aritmil must be administered by infusion, since even a very slow injection of the drug can cause severe hypotension, acute cardiovascular failure, or severe respiratory failure. If circulatory collapse occurs, atropine may be effective.
Intravenous administration of amiodarone by syringe in the form of injections is possible only in emergency situations when there are no other therapeutic options, and only in cardiac intensive care units with constant ECG monitoring.
Do not mix in the same syringe or system with other medicines!
Aritmil solution contains benzyl alcohol, which can cause toxic and allergic reactions in children under 3 years of age.
Before surgery, it is imperative to warn the anesthesiologist that the patient has received/is receiving amiodarone (risk of respiratory distress syndrome).
To prevent undesirable effects, concomitant therapy must be carefully prescribed, taking into account clinically significant interactions with amiodarone.
Amiodarone has a low proarrhythmic effect, which is manifested mainly when used together with drugs that prolong the period of ventricular repolarization or in case of electrolyte imbalance (especially hypokalemia). It is advisable to correct electrolyte imbalance before starting the administration of Aritmil.
During treatment with amiodarone, ECG changes are possible: prolongation of the Q-T interval (due to prolonged repolarization), appearance of a U wave, deformation of the T wave. These changes are not a manifestation of drug toxicity.
During treatment with Aritmil, it is recommended to regularly check liver function (transaminase activity) for early detection of liver damage, since in the first 24 hours of intravenous administration of the drug, severe hepatocellular insufficiency, sometimes fatal, may occur.
Use with caution in the elderly, patients taking 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 Aritmil should be discontinued, beta-adrenomimetics or glucagon may be used, and if necessary, cardiac pacing.
The drug should also be used with caution in cases of hypotension, asthma, severe respiratory failure, decompensated cardiomyopathy or severe heart failure, and liver failure.
When using the drug in patients with diabetes, it should be remembered that Aritmil is administered only in a 5% glucose solution.
If a diagnosis of interstitial pneumonitis is suspected, it is necessary to conduct a chest X-ray and decide whether to discontinue the drug and prescribe corticosteroids.
In some cases, patients receiving amiodarone have experienced acute distress syndrome immediately after surgery. Careful monitoring of such patients is recommended when using mechanical ventilation. Before surgery, the anesthesiologist should be informed that the patient has received this drug.
Aritmil contains iodine (200 mg of the drug contains 75 mg of iodine), so it can affect the results of tests for the accumulation of radioactive iodine in the thyroid gland, but does not affect the level of hormones T3, T4, TSH. Amiodarone can cause thyroid dysfunction, especially in patients with a history of its dysfunction (including family history). Therefore, before starting, during treatment and for several months after its completion, it is necessary to conduct careful clinical and laboratory monitoring of thyroid function.
It is not recommended to use Aritmil with beta-blockers (except sotalol and esmolol), some calcium channel blockers (verapamil, injectable form of diltiazem), laxatives that stimulate intestinal motility and can cause hypokalemia. Also, with simultaneous use of Aritmil and flecainide, it is necessary, taking into account the increase in plasma levels of the latter, 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).
Side effects of the drug are usually dose-dependent, so care should be taken to determine the minimum effective maintenance dose to prevent or minimize the risk of adverse effects.
Use during pregnancy and breastfeeding. Since the drug affects the thyroid gland of the fetus, the use of the drug during pregnancy is contraindicated. Amiodarone is excreted in breast milk in significant quantities, therefore, if necessary, the drug should be used in breastfeeding women, breastfeeding should be discontinued during treatment.
Children. The use of the drug is contraindicated in children under 3 years of age.
Aritmil solution contains benzyl alcohol, which can cause toxic and allergic reactions in children under 3 years of age.
Ability to influence the reaction rate when driving vehicles or working with other mechanisms. The drug may negatively affect the reaction rate when driving vehicles or working with other mechanisms, therefore, during the period of treatment, you should refrain from driving vehicles and engaging in potentially dangerous activities.
Tablets and solution for injection. Concomitant use with drugs that can cause polymorphic paroxysmal ventricular tachycardia of the pirouette type ("torsade de pointes") due to prolongation of the QT interval is contraindicated:
antiarrhythmic drugs, including class IA drugs (quinidine, hydroquinidine, procainamide, disopyramide), class III (dofetilide, ibutilide), sotalol, bepridil; drugs that do not have antiarrhythmic activity, including vincamine, cisapride, erythromycin (iv), spiramycin (iv), vincamine (iv), co-trimazole, pentamidine in the case of parenteral administration, since there is a risk of developing paroxysmal tachycardia with a fatal outcome; neuroleptics: some phenothiazine neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine); benzamides (amisulpride, sultopride, sulpiride, tiapride), butyrophenones (droperidol, galaperidol), pimozide, sertindole; lithium and tricyclic antidepressants (doxepin, maprotiline, amitriptyline, trazodone); some antihistamines (loratadine, terfenadine, astemizole, mizolastine); antimalarials (quinine, mefloquine, chloroquine, halofantrine); moxifloxacin, sparfloxacin.
Combination therapy with the following drugs is not recommended:
beta-blockers (except sotalol and esmolol) and some calcium channel blockers (verapamil, injectable form of diltiazem), since disturbances in automaticity (marked bradycardia), conduction (AV-blockade) and contractility of the heart may occur due to inhibition of sympathetic compensatory mechanisms. If such a combination is unavoidable, careful preliminary control of the QT interval and constant ECG monitoring during treatment are necessary; fluoroquinolones (except moxifloxacin, sparfloxacin, the combination with which is contraindicated) - paroxysmal tachycardia of the "torsade de pointes" type may occur. If such a combination is unavoidable, careful preliminary control of the QT interval and constant ECG monitoring are necessary.
The following drugs are prescribed with caution in combination with Aritmil.
Agents that cause hypokalemia and thus increase the risk of developing torsade de pointes:
diuretics that cause hypokalemia (alone or with other drugs); corticosteroids (glucocorticoids, mineralocorticoids); tetracosactide; amphotericin B (iv); laxatives that stimulate intestinal motility.
It is necessary to prevent the occurrence of hypokalemia and, if necessary, correct it; monitor the QT interval and the appearance of U waves on the ECG. It is permissible to increase the Q-TS interval to 450 ms or no more than 25% of the initial value.
In the event of paroxysmal tachycardia of the torsade de pointes type, do not use antiarrhythmic drugs, but use intravenous administration of magnesium sulfate solution or cardiac pacing aimed at reducing the heart rate.
oral anticoagulants
The enhanced effect of oral anticoagulants and the increased risk of bleeding dictate the need for more frequent monitoring of prothrombin levels in the blood and correction of anticoagulant doses during treatment with amiodarone and after drug withdrawal.
Oral forms of diltiazem
Risk of bradycardia and AV block, especially in the elderly. Clinical and ECG monitoring of the patient's condition is necessary.
cardiac glycosides
Disturbances of automaticity (marked bradycardia) and AV conduction (synergism of action) may occur; in addition, an increase in the concentration of digoxin in the blood plasma is possible (as a result of a decrease in digoxin clearance).
Clinical, ECG and laboratory monitoring (including, if possible, determination of plasma digoxin levels) is necessary; it may be necessary to change the dose of cardiac glycosides.
esmolol
Possible violation of automatism, conduction and contractile properties of the heart due to suppression of sympathetic compensatory mechanisms. Clinical and ECG monitoring of the patient's condition is necessary.
phenytoin
Increased plasma levels of phenytoin with symptoms of overdose (including neurological) are possible. Clinical monitoring and dose reduction of phenytoin are necessary if signs of overdose appear; if possible, determination of plasma levels of phenytoin.
clopidogrel
Amiodarone is an inhibitor of CYP 3A4, increasing plasma levels of other drugs that are metabolized by this enzyme. Since clopidogrel is metabolized to its active form by CYP 3A4, concomitant use of amiodarone may result in ineffective inhibition of platelet aggregation.
Drugs metabolized by the cytochrome P450 3A4 system
Their simultaneous use with amiodarone, which is an inhibitor of this enzyme, increases the concentration of these drugs in the blood plasma, and, as a result, their toxicity may increase:
cycle
