Pharmacological properties
Pharmacodynamics. Antiarrhythmic properties. Prolongation of phase III 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 suppression 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 an acceleration of the 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 AV conduction pathways.
Other properties: 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, which included 6553 patients who had recently suffered a myocardial infarction (78%) or with chronic heart failure (22%).
The mean duration of follow-up of patients ranged from 0.4 to 2.5 years. The mean daily maintenance dose ranged from 200 to 400 mg.
This meta-analysis showed that amiodarone statistically significantly reduced overall mortality by 13% (95% confidence interval (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 to 1% in the placebo group. Hyperthyroidism was diagnosed in 1.4% of patients in the amiodarone group compared to 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 in children:
- loading dose: 10-20 mg kg/day for 7-10 days (i.e. 500 mg/m2/day in terms of body surface area);
- maintenance dose: the minimum effective dose should be used; 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.
Bioavailability when taken orally, depending on the individual characteristics of the patient, can be 30-80% (on average - 50%). After a single dose of the drug, C max in blood plasma is achieved within 3-7 hours.
Therapeutic activity is manifested on average within 1 week of taking the drug (from several days to 2 weeks).
T ½ of amiodarone is long and characterized by significant interindividual variation (from 20 to 100 days). During the first days of treatment, the drug accumulates in most body tissues, especially in adipose tissue. Elimination begins after a few days, and the ratio of drug intake to excretion reaches equilibrium within one or several 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.
Part of the iodine is separated from the compound and excreted in the urine as iodide; when using amiodarone in a daily dose of 200 mg, the excretion of iodine is 6 mg / 24 hours. The remaining compound and, accordingly, most of the iodine are excreted in the feces after hepatic transport.
Since only a small amount of the drug is excreted 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 manifest itself for a period of 10 days to 1 month.
Amiodarone is primarily metabolized by cytochrome CYP 3A4 and also by cytochrome CYP 2C8. Amiodarone and its metabolite, desethylamiodarone, are potent in vitro inhibitors of cytochrome CYP 1A1, CYP 1A2, CYP 2C9, CYP 2C19, CYP 2D6, CYP 3A4, CYP 2A6, CYP 2B6, and CYP 2C8. Amiodarone and desethylamiodarone may inhibit the function of transport proteins such as P-glycoprotein and organic cation transporter type 2. One study reported a 1.1% increase in creatinine (a substrate for organic cation transporter type 2).
In vivo data suggest an interaction between amiodarone and substrates of CYP 3A4, CYP 2C9, CYP 2D6 and P-glycoprotein.
Pediatric population: No controlled clinical studies have been conducted in children. Limited data available do not indicate differences in pharmacokinetics 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 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
pills
Prevention of relapses:
- ventricular tachycardia, which poses a threat to the patient's life: treatment must be started in a hospital setting with constant monitoring of the patient's condition;
- symptomatic ventricular tachycardia (documented) that leads to incapacity;
- supraventricular tachycardia (documented) requiring treatment, and in cases where other drugs do not have a therapeutic effect or are contraindicated;
- ventricular fibrillation.
Treatment of supraventricular tachycardia: slowing or reducing atrial fibrillation or flutter.
CHD and/or left ventricular dysfunction (see Pharmacodynamics).
Solution for injection
Treatment with the drug should be initiated and, as a rule, monitored only in a hospital setting or under the supervision of a specialist. Cordarone for intravenous administration is intended only for the treatment of severe heart rhythm disorders in patients who do not respond to other therapies, or in cases where other treatments cannot be used.
Tachyarrhythmias associated with Wolff-Parkinson-White syndrome.
Tachyarrhythmias of all types, including supraventricular, nodal and ventricular tachycardias; atrial flutter and fibrillation, ventricular fibrillation; in cases where other drugs cannot be used.
Cordarone for intravenous administration can be used when a rapid response to treatment is required or when oral administration of the drug is not possible.
Application
pills
Initial treatment. The recommended dose 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 and under ECG control.
Maintenance therapy. The minimum effective dose should be used. Depending on the patient's response to the drug, the maintenance dose may range from ½ tablet per day (1 tablet every 2 days) to 2 tablets per day.
Solution for injection
For reasons related to the dosage form of the drug, it is necessary to use concentrations not less than the equivalent of 2 ampoules per 500 ml. Cordarone can be administered only in isotonic (5%) glucose solution.
Do not dilute the drug with isotonic sodium chloride solution, as precipitate formation is possible!
Do not mix with other drugs in the same infusion system.
Cordarone for intravenous administration should be used only when the necessary equipment for monitoring cardiac function, defibrillation, and pacing is available.
Cordarone for intravenous administration can be used before performing direct current cardioversion.
Amiodarone should be administered via central venous access, except in cases of cardiopulmonary resuscitation for ventricular fibrillation resistant to electric defibrillation in patients with cardiac arrest - in these circumstances, peripheral access may be used if it is not possible to provide central venous access (see Features of use).
Severe cardiac arrhythmias in which oral administration of the drug is unacceptable, except in cases of cardiopulmonary resuscitation for ventricular fibrillation resistant to electro-defibrillation in patients with cardiac arrest.
Infusion through central venous access
Maintenance dose: 10-20 mg/kg/day (average 600-800 mg/day to 1.2 g/day) in 250 ml of glucose solution for several days.
The transition to oral therapy (3 tablets per day) should begin on the first day of infusion therapy. It can be increased to 4 or even 5 tablets per day.
Cardiopulmonary resuscitation in case of ventricular fibrillation resistant to electric defibrillation in patients with cardiac arrest. When using the drug in such a situation, it is recommended to use a central venous catheter (if available and ready), otherwise the drug can be administered through peripheral veins, using the largest peripheral vein with maximum blood flow if possible.
The initial dose is 300 mg (or 5 mg/kg body weight), administered diluted in 20 ml of 5% glucose solution by rapid injection. If ventricular fibrillation persists, an additional 150 mg (or 2.5 mg/kg body weight) of the drug can be administered.
Do not add any other agents to the syringe.
Pediatric Population: The safety and efficacy of amiodarone in children have not been established. Due to the benzyl alcohol content, amiodarone for intravenous administration is contraindicated in premature and full-term newborns, infants, and children under 3 years of age (see Adverse Reactions and Precautions).
Contraindication
Hypersensitivity to iodine, amiodarone or other components of the drug.
Sinus bradycardia, sinoatrial heart block in the absence of an endocardial pacemaker (artificial pacemaker).
Sick sinus syndrome in the absence of an endocardial pacemaker (risk of sinus node arrest).
High-grade AV conduction disturbances in the absence of an endocardial pacemaker.
Hyperthyroidism - as the disease may worsen while taking amiodarone.
Vascular insufficiency (vascular collapse).
Severe arterial hypotension.
Age up to 3 years (due to the presence of benzyl alcohol).
II and III trimesters of pregnancy.
Breastfeeding period.
Concomitant use with drugs that may cause torsades de pointes-type paroxysmal tachycardia (except antiparasitic drugs, neuroleptics and methadone):
- class Ia antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
- class III antiarrhythmic drugs (sotalol, dofetilide, ibutilide);
- other drugs such as arsenic compounds, e.g. bepridil, cisapride, citalopram, escitalopram, diphemanil, dolasetron for IV administration, domperidone, dronedarone, erythromycin for IV administration, levofloxacin, mequitazine, mizolastine, moxifloxacin, prucalopride, spiramycin for IV administration, toremifene, vincamine for IV administration (see Interaction with other drugs);
- telaprevir;
- cobicistat.
These contraindications do not apply to the use of amiodarone for cardiopulmonary resuscitation in cardiac arrest resulting from ventricular fibrillation and resistant to external electrical pulse therapy.
Side effects
Side effects are classified by organ system and frequency of occurrence:
very common (10%); common (1%, 10%); uncommon (0.1%, 1%); rare (0.01%, 0.1%); very rare (0.01%).
From the organ of vision. Very common. Microdeposits in the cornea, in almost all adults, usually within the subpupillary area, which do not require withdrawal of amiodarone. In exceptional cases, they are associated with colored halos in bright light or with blurred vision.
Corneal microdeposits are complex lipid deposits and are always fully reversible after discontinuation of the drug.
Very rare. Optic neuropathy (optic neuritis), which may progress to complete blindness, and, according to the results of fundus examination, with swelling of the optic nerve head, may progress to more or less severe reduction in visual acuity. The causal relationship of this adverse event to amiodarone has not yet been established. However, in the absence of other obvious reasons for the development of this adverse event, it is recommended to cancel amiodarone.
Skin and subcutaneous tissue disorders: Very common: Photosensitivity. It is recommended to avoid exposure to sunlight (and ultraviolet radiation in general) during treatment.
Often. Skin pigmentation of a bluish or bluish-gray color, which occurs against the background of prolonged use of high daily doses and slowly disappears after discontinuation of the drug (within 10-24 months).
Very rare: Erythema following radiotherapy. Skin rashes, usually non-specific. Exfoliative dermatitis, although a causal relationship of this adverse event to the drug has not been clearly established. Alopecia.
endocrine disorders
On the part of the endocrine system. Side effects on the part of the thyroid gland.
Often. Hypothyroidism causes typical symptoms: weight gain, cold intolerance, apathy, drowsiness. A significant increase in TSH levels confirms this diagnosis. After discontinuation of treatment, normal thyroid function gradually returns over a period of 1 to 3 months. Drug withdrawal is not required: if amiodarone is necessary, treatment with this drug can be continued in combination with thyroid hormone replacement therapy with levothyroxine. L-thyroxine doses can be adjusted depending on TSH levels.
Hyperthyroidism is more difficult to diagnose: symptoms are less pronounced (slight unexplained weight loss, insufficient effectiveness of antianginal and/or antiarrhythmic drugs); elderly patients have mental symptoms, even thyrotoxicosis.
A significant decrease in high-sensitivity TSH levels confirms this diagnosis. In such cases, amiodarone must be discontinued, which is usually sufficient to achieve clinical normalization within 3-4 weeks. Since severe cases of this adverse event can be fatal, appropriate therapy must be initiated promptly.
If the cause of the problems is thyrotoxicosis (either directly or through its effects on the vulnerable balance of the myocardium), the variability in the efficacy of synthetic antithyroid drugs makes it necessary to recommend the use of corticosteroids in high doses (1 mg/kg) for a fairly long period (3 months). Cases of hyperthyroidism lasting up to several months after discontinuation of amiodarone have been reported.
Other endocrine disorders: Very rare cases of syndrome of inappropriate antidiuretic hormone secretion, especially when amiodarone is used concomitantly with drugs that can induce hyponatremia (see Research results).
Respiratory, thoracic and mediastinal disorders: Common: Diffuse interstitial or alveolar pneumonitis and bronchiolitis obliterans with sclerotic pneumonia have been reported, sometimes fatal. The appearance of dyspnea on exertion or dry cough, either alone or in association with worsening general condition (fatigue, weight loss and slight fever), requires radiological examination and, if necessary, discontinuation of the drug, as these lung diseases can lead to pulmonary fibrosis.
Early withdrawal of amiodarone with or without corticosteroid therapy results in gradual resolution of symptoms. Clinical signs usually resolve within 3–4 weeks, with improvement in radiographic and pulmonary function occurring more slowly (over several months).
Employees of the State Traffic Safety Inspectorate recorded several cases of pleurisy, usually associated with interstitial pneumopathy.
Very rare: Bronchospasm in patients with acute respiratory failure, especially in patients with bronchial asthma. Acute respiratory distress syndrome, in some cases fatal, sometimes in the early period after surgery (a possible interaction with high doses of oxygen was suspected) (see Special warnings and precautions for use).
Frequency not known (cannot be estimated from the available data). Cases of pulmonary haemorrhage, sometimes presenting as haemoptysis, have been reported. These pulmonary adverse events are often associated with amiodarone-induced pneumopathy.
Nervous system disorders: Common: Tremor or other extrapyramidal symptoms. Sleep disturbances, including nightmares. Peripheral sensory-motor or mixed peripheral neuropathy.
Uncommon. Myopathy. Peripheral sensory, motor or mixed neuropathy and myopathy may develop after a few months of treatment, but sometimes they occur after several years. These adverse events are usually reversible after discontinuation of treatment. However, recovery may be incomplete, very slow and may not be achieved until several months after discontinuation of the drug.
Very rare: Cerebellar ataxia. Benign intracranial hypertension, headache. If a headache occurs, an examination should be performed to determine its possible cause.
Hepatobiliary disorders: Cases of liver damage, diagnosed by elevated serum transaminase levels, have been reported. The following adverse reactions have been reported. Very common: Usually a moderate and isolated increase in transaminase levels (1.5-3 times the upper limit of normal), which disappeared after discontinuation of the drug or even spontaneously.
Very rare. Chronic liver damage requiring long-term treatment. Histological changes correspond to the picture of pseudoalcoholic hepatitis or cirrhosis of the liver. Since clinical and laboratory signs are not clearly expressed (variability of hepatomegaly, increased transaminase levels in the blood 1.5-5 times higher than normal), regular monitoring of liver function is indicated. In the event of an increase in transaminase levels in the blood, even moderate, occurring after taking the drug for more than 6 months, it is necessary to suspect the development of chronic liver damage. These clinical and biological changes usually disappear after discontinuation of the drug. The State Traffic Safety Inspectorate has recorded several reversible cases of such changes.
Cardiac disorders: Common: Bradycardia, usually moderate and dose-dependent.
Uncommon: Myocardial conduction disturbances (sinoatrial block, AV block of varying degrees).
Very rare: Severe bradycardia and, exceptionally, sinus arrest have been reported in a few cases (on the background of sinus node dysfunction, in elderly patients). Occurrence or worsening of existing arrhythmia, sometimes accompanied by cardiac arrest.
Frequency unknown: Paroxysmal ventricular tachycardia of the torsade de pointes type.
Gastrointestinal disorders: Very common: Mild digestive disorders (nausea, vomiting, dysgeusia), usually occurring at the beginning of treatment and disappearing after dose reduction.
Frequency unknown: Pancreatitis/acute pancreatitis.
Breast and reproductive system disorders. Very rare. Epididymitis. The causal relationship of this adverse event to the use of this medicinal product has not been clearly established.
Vascular disorders: Very rare: Vasculitis.
Research findings: Rare: Rare cases of hyponatremia may indicate the development of the syndrome of inappropriate antidiuretic hormone secretion.
Very rare: Kidney damage with moderate increase in creatinine level.
Blood and lymphatic system disorders: Very rare: Thrombocytopenia.
Immune system disorders: Frequency not known (cannot be estimated from the available data). Cases of angioedema and/or urticaria have been reported.
General disorders: Frequency not known: Granuloma, mainly bone marrow granuloma, has been reported.
Special instructions
Cardiac effects: Before starting the drug, an ECG should be performed and the level of potassium in the blood plasma should be determined.
In elderly patients, the slowing of the heart rate may increase while taking the drug.
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.
The occurrence of second or third degree AV block, sinoatrial block or bifascicular block during treatment requires discontinuation of the drug. The development of first degree AV block requires increased monitoring of the patient.
Cases of new arrhythmia or worsening of existing arrhythmias being treated have been reported (see Adverse Reactions).
This proarrhythmic effect may be particularly pronounced in the presence of factors that contribute to QT prolongation, including certain drug combinations and hypokalemia (see Adverse Reactions and Interactions). 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.
Thyroid disorders. This medicinal product contains iodine and therefore 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.
Amiodarone may cause thyroid dysfunction, especially in patients with a history of thyroid dysfunction. Quantitative determination of TSH is recommended in all patients before starting 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 Adverse Reactions).
Pulmonary disorders: The appearance of dyspnea or nonproductive cough, either isolated or associated with worsening of the general condition, should be considered as a possible sign of pulmonary toxicity of the drug, for example, the development of interstitial pneumonitis, and a radiological examination of the patient is required (see Adverse Reactions).
Liver disorders: Regular monitoring of liver function is recommended at the beginning of treatment with amiodarone and periodically thereafter (see Adverse Reactions).
Neuromuscular disorders: Amiodarone may cause peripheral sensory-motor or mixed neuropathy and myopathy (see Adverse Reactions).
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. Therefore, concomitant use of these drugs with amiodarone is not recommended.
If concomitant use of these drugs with amiodarone can be avoided, then patients should be closely monitored when initiating treatment with sofosbuvir alone or in combination with other direct-acting antivirals. Patients with a known high risk of bradyarrhythmia should be under appropriate continuous monitoring for at least 48 hours after starting treatment with sofosbuvir.
Due to the long T½ 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 antiviral drugs.
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 informed that in case of their occurrence, it is necessary to seek emergency medical attention.
Disorders associated with interactions with other drugs. Combinations (see Interactions with other drugs) with drugs such as:
- β-adrenergic blockers, except sotalol (contraindicated combination) and esmolol (combination requiring precautions for use);
- verapamil and diltiazem - should only be considered for the prevention of life-threatening ventricular arrhythmias.
The concomitant use of amiodarone is not recommended with the following drugs:
cyclosporine, diltiazem (for injection) or verapamil (for injection), some antiparasitics (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 Interactions with other drugs).
Excipient-related disorders: This medicinal product contains lactose and is therefore not recommended for use in patients with galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases).
Electrolyte disturbances, especially hypokalemia. It is important to consider any situation in which the patient may be at risk of hypokalemia, as hypokalemia may provoke proarrhythmic effects. Hypokalemia should be corrected before initiating amiodarone.
Side effects, such as these, are most often associated with excessive drug intake and can be avoided or minimized by careful adherence to the minimum maintenance dose.
During treatment, patients are advised to avoid sun exposure or take protective measures against sun exposure.
The safety and efficacy of amiodarone for the treatment of children have not been evaluated in controlled clinical trials.
Due to the possible increase in the defibrillation threshold and/or stimulation threshold in patients with implanted cardiac defibrillators or pacemakers, it is necessary to check this threshold before using amiodarone and several times after starting its use, as well as each time the dose of the drug is adjusted.
Anesthesia: The anesthesiologist should be informed before surgery that the patient is taking amiodarone.
Adverse effects of chronic amiodarone treatment may increase 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 reported in the early postoperative period in patients receiving amiodarone. Therefore, it is recommended that such patients be closely monitored during mechanical ventilation (see Adverse Reactions).
Use during pregnancy and lactation. Pregnancy. No teratogenic effects have been observed in animal studies, therefore no malformative effects are expected in humans. To date, substances that cause malformations in humans have been shown to be teratogenic in animals in carefully conducted studies in two species.
There are insufficient clinical data to assess the possible teratogenic or fetotoxic effects of amiodarone when administered in therapeutic doses during the first trimester of pregnancy.
Excessive amounts of iodine entering the body when using this medication during the period of taking the drug can lead to hypothyroidism in the fetus or even the development of the clinical picture of fetal hypothyroidism (goiter).
Given the effect of amiodarone on the fetal thyroid gland, this drug is contraindicated for use during pregnancy, except in cases where the benefit to the mother outweighs the risk to the fetus.
Breastfeeding. Amiodarone and its metabolites, together with iodine, are excreted in breast milk in quantities exceeding those found in maternal plasma. Given the risk of hypothyroidism in the newborn, breastfeeding is contraindicated during treatment with amiodarone.
Children: The safety and efficacy of amiodarone in children have not been evaluated, therefore its use in children is not recommended.
The ability to influence the reaction rate when driving vehicles or working with other mechanisms. The possibility of developing adverse reactions from the nervous system and the organ of vision should be taken into account.
Interactions
Antiarrhythmic drugs. Many antiarrhythmic drugs inhibit cardiac automaticity, conduction, and myocardial contractility.
Concomitant use of antiarrhythmics from different classes may be beneficial, but in most cases, treatment with such a combination requires careful clinical and ECG monitoring. Concomitant use of antiarrhythmics that can induce torsades de pointes (such as amiodarone, disopyramide, quinidine compounds, sotalol, etc.) 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.
The simultaneous use of amiodarone with drugs that have a negative inotropic effect, cause bradycardia and / or slow AV conduction, therefore requires careful clinical and ECG monitoring.
Drugs that can induce torsades de pointes. This serious arrhythmia can be induced by certain drugs, whether or not they are antiarrhythmic drugs. Predisposing factors include hypokalemia (see Drugs that lower potassium levels), bradycardia (see Drugs that slow the heart rate), or congenital or acquired preexisting QT prolongation.
Drugs that may contribute to the development of torsades de pointes include, in particular, class Ia and III antiarrhythmic drugs and some neuroleptics. For dolasetron, erythromycin, spiramycin and vincamine, this interaction occurs only when using dosage forms for intravenous administration.
The simultaneous use of two drugs, each of which is a torsades de pointes-inducing drug, 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 agents that cause the occurrence of torsades de pointes.
Drugs that slow the heart rate. Many drugs can cause bradycardia, including class Ia antiarrhythmic drugs, β-adrenergic blockers, some class III antiarrhythmic drugs, some calcium channel blockers, digitalis drugs, pilocarpine, and anticholinesterase drugs.
Effects of Amiodarone on Other Medicinal Products: Amiodarone and/or its metabolite, desethylamiodarone, inhibit CYP 1A1, CYP 1A2, CYP 3A4, CYP 2C9, CYP 2D6, and P-glycoprotein and may increase exposure to their substrates. Given the long duration of action of amiodarone, such interactions may occur for several months after discontinuation of amiodarone treatment.
Effects of other medicinal products on amiodarone: CYP 3A4 and CYP 2C8 inhibitors may inhibit the metabolism of amiodarone and thus increase its exposure.
CYP 3A4 inhibitors (e.g. grapefruit juice and some medications) should generally not be used during treatment with amiodarone.
Contraindicated combinations (see Side effects). Drugs that may induce torsades de pointes (except antiparasitic drugs, neuroleptics and methadone (see Not recommended combinations):
- class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide);
- class III antiarrhythmics (dofetilide, ibutilide, sotalol);
- 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.
Increased risk of developing ventricular arrhythmias, especially torsades de pointes.
Telaprevir. Cardiac automatism and conduction disorders
