Amiodarone 0.2 g tablets # 30

Amiodarone (AMIODARONE) instructions for use

Composition

active ingredient: 1 tablet contains amiodarone hydrochloride (in terms of 100% substance) 200 mg
auxiliary substances: corn starch, lactose, sodium croscarmellose, silicon dioxide colloid, magnesium stearate.

Dosage form

Pills.

Pharmacological group

Antiarrhythmic drugs of the III class. Amiodarone. The code of automatic telephone exchange С01B D01.

Indications

Relapse prevention:

• ventricular tachycardia, which is a threat to the life of the patient: treatment must begin in a hospital with constant monitoring of the patient's condition;
• symptomatic ventricular tachycardia (documented), which leads to disability;
• supraventricular tachycardia (documented), which requires treatment, and in cases where other drugs have no therapeutic effect or are contraindicated;
• ventricular fibrillation.

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

Ischemic heart disease and / or impaired left ventricular function.

Contraindications

Sinus bradycardia, sinoatrial heart block in the absence of an endocardial pacemaker (artificial pacemaker).

Syndrome of weakness of the sinus node in the absence of an endocardial pacemaker (risk of stopping the sinus node).

Violation of AV conduction of high degree in the absence of an endocardial pacemaker. Thyroid dysfunction.

Hypersensitivity to iodine, amiodarone or to any component of the drug.

Combination with drugs that can cause a paroxysmal ventricular tachycardia of the torsade de pointes type

• antiarrhythmics of class Ia (quinidine, hydroquinidine, disopyramide)
• antiarrhythmic drugs of the III class (sotalol, dofetilida, ibutilid)
• other drugs such as arsenic compounds, bepridil, cisapride, difemanyl, dolasatron (intravenously), erythromycin (intravenously), misolastine, vincamine (intravenously), moxifloxacin, spiramycin (c), toremifene, some antipsychotics (see "interaction with other drugs and other types of interactions ").

Dosing and Administration

The beginning of treatment. The recommended dose for adults is 200 mg 3 times a day for 8-10 days.

In some cases, higher doses (4-5 tablets per day) are used at the beginning of treatment, but always - for a short time and under electrocardiographic control.

Supportive treatment. A minimally effective dose should be used. Depending on the reaction of the patient to the use of the drug, the maintenance dose can be from ½ tablets per day (1 tablet every two days) to 2 tablets per day.

Adverse Reactions

From the side of the organs of sight.

Microdeposition in the cornea, almost in all adults, usually within the area under the pupil, which does not require the abolition of amiodarone. In exceptional cases, they are associated with the colored halos in dazzling light or with blurred vision.

Microdeposits in the cornea are complex lipid deposits and are always completely reversible after drug discontinuation.

Neuropathy of the optic nerve (optic neuritis), which can progress to complete blindness, as well as from the examination of the fundus, may be with the edema of the nipple of the optic nerve, can progress to a more or less severe reduction in visual acuity. The causal relationship of this side effect with the administration of amiodarone has not been established to date. However, in the absence of other obvious reasons for the development of this side effect, it is recommended to cancel amiodarone.

From the skin and subcutaneous tissue.

Photosensitivity. It is recommended to avoid exposure to solar radiation (and ultraviolet radiation in general) during treatment.

Pigmentation of the skin is cyanotic or bluish gray, which occurs against the background of long-term use of high daily doses of the drug and slowly disappear after the drug is discontinued (within 10-24 months).

Erythema in the background of radiation therapy. Skin rashes, usually nonspecific. Exfoliative dermatitis, although the causal relationship of this side effect with taking the drug to date is not clearly established. Alopecia. Hives.

From the side of the thyroid gland.

Some "discrepancy" of the level of thyroid hormones (an increase in the level of T4 with a normal or slightly reduced TC level), in the absence of clinical signs of thyroid dysfunction does not require discontinuation of treatment.

Hypothyroidism causes typical symptoms: weight gain, cold intolerance, apathy, drowsiness. A significant increase in the level of thyroid-stimulating hormone (TSH) confirms this diagnosis. Euthyroidism is usually achieved within 1-3 months after discontinuation of the drug. The withdrawal of the drug is not necessary: in the case when the use of amiodarone is justified, treatment with this drug may continue in combination with hormone replacement hormone therapy with thyroid hormones using levothyroxine. Doses of levothyroxine can be adjusted depending on the levels of TSH.

Hyperthyroidism is more difficult to diagnose, as the symptoms are less pronounced (small causeless weight loss, insufficient effectiveness of antianginal and / or antiarrhythmic drugs); in elderly patients there are mental symptoms, even thyrotoxicosis.

A significant reduction in the levels of highly sensitive TSH confirms this diagnosis. In this case, it is necessary to cancel amiodaron, which, as a rule, is enough for the onset of clinical normalization for 3-4 weeks. Since serious cases of this side effect can be lethal, it is necessary to begin promptly appropriate therapy.

If the cause of the problem is thyrotoxicosis (both directly and through its effect on the vulnerable balance of the myocardium), the variability in the effectiveness of synthetic antithyroid drugs necessitates recommending the administration of high doses of corticosteroids (1 mg / kg) for a sufficiently long time (3 months) .

Reported cases of hyperthyroidism within a few months after the abolition of amiodarone.

Very rare cases of SNSAG (syndrome of inappropriate secretion of ADH), especially if the drug is used simultaneously with drugs that can induce hyponatremia. See "Research results".

From the respiratory system.

There were cases of diffuse interstitial or alveolar pneumopathy and obliterating bronchiolitis with pneumonia, sometimes with a fatal outcome. The appearance of dyspnoea with physical exertion or dry cough, both isolated and associated with worsening of the general state of health (increased fatigue, decreased body weight and a slight increase in body temperature), requires an X-ray examination and, if necessary, drug withdrawal, as these lung diseases can lead to pulmonary fibrosis.

Early cancellation of amiodarone, along with the administration of corticosteroid therapy or without it, lead to a gradual disappearance of symptoms. Clinical signs usually disappear within 3-4 weeks of improving the radiographic pattern and pulmonary function is slower (for several months).

Several cases of pleurisy, commonly associated with interstitial pneumopathy, have been reported.

Bronchospasm in patients with acute respiratory failure, especially in patients with bronchial asthma. Acute respiratory distress syndrome, in some cases - with a lethal outcome, sometimes in the early postoperative period after surgical intervention (it was suspected that interaction with high doses of oxygen could be possible) (see Section "Features of application").

Cases of pulmonary hemorrhage, which in some cases may be manifested by hemoptysis, have been reported. These pulmonary side effects are often associated with amiodarone-induced pneumopathy.

From the side of the central nervous system.

Tremor or other extrapyramidal symptoms. Sleep disturbance, including nightmares. Sensory, motor or mixed peripheral neuropathy.

Myopathy. Sensory, motor or mixed peripheral neuropathy and myopathy can develop after several months of treatment, but sometimes they occur after several years. These side effects are usually reversible after drug withdrawal. However, recovery may be incomplete, very slow and can be observed only a few months after discontinuation of the drug.

Cerebellar ataxia. Benign intracranial hypertension, headache. When rare headaches occur, a survey should be performed to determine their possible cause.

From the digestive system.

Reported cases of liver damage, these cases were diagnosed by elevated levels of transaminases in the serum. The following adverse events have been reported.

Usually a moderate and isolated increase in the level of transaminases (1.5-3 times higher than normal), which disappeared after drug withdrawal or even spontaneously.

Acute liver damage with increased transaminase levels in the blood and / or jaundice, including liver failure, sometimes lethal, which requires withdrawal of the drug.

Chronic liver damage, which requires long-term treatment. Histological changes correspond to the picture of pseudo-alcoholic hepatitis or cirrhosis of the liver. Since clinical and laboratory signs are not clearly expressed (variability of hepatomegaly, an increase in the level of transaminases 1.5-5 times more than normal), regular monitoring of liver function is indicated. In case of an increase in the level of transaminases in the blood, even mild, 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 the drug is discontinued. There are several cases of irreversible consequences.

Cardiac disorders.

Bradycardia, usually mild and dose-dependent.

Violation of the conductivity of the myocardium (sinoatrial blockade, AV-blockade of various degrees).

Pronounced bradycardia and, in exceptional cases, failure of the sinus node, reported in several cases (against a sinus node dysfunction, in elderly patients). The occurrence or complication of an existing arrhythmia, which is sometimes accompanied by cardiac arrest.

Paroxysmal ventricular tachycardia torsade de pointes.

From the digestive tract.

Minor digestive disorders (nausea, vomiting, dysgeusia), which usually occur at the beginning of treatment and disappear after a dose reduction.

Influence on the reproductive system and mammary glands.

Epididymitis. The causal relationship of this side effect with the use of this medication has not been clearly established to date. Impotence.

From the side of the vascular system.

Vasculitis.

Results of the research.

Rare cases of hyponatremia may indicate the development of SNSAG.

Kidney damage with a moderate increase in the level of creatinine.

From the system of the blood and lymphatic system.

Hemolytic and aplastic anemia, thrombocytopenia.

From the immune system.

There have been reports of cases of angioedema.

Overdose

Information about an overdose of amiodarone is limited. There have been reports of single cases of sinus bradycardia, ventricular arrhythmias, in particular ventricular torsades de pointes, and liver damage. Treatment should be symptomatic. Given the pharmacokinetic profile of the drug, it is recommended to monitor the patient's condition for a long period, especially the heart.

Amiodarone and its metabolites are excreted by dialysis.

Use during pregnancy and lactation

Pregnancy. Given the effect on the thyroid of the fetus, amiodarone is contraindicated during pregnancy, unless the use exceeds the risk.

Breastfeeding. Amiodarone penetrates into breast milk in large quantities, so breast-feeding is contraindicated during treatment with amiodarone.

Children

The drug is not used in children.

Application features

Effects from the heart. Before starting the drug, you need to make an ECG and determine the potassium level in the blood serum.

In elderly patients, the slowing of the heart rate may increase with the use of the drug.

Amiodarone induces changes in the ECG. These kordaron-induced changes include prolongation of the QT interval due to prolonged repolarization with the possible appearance of a U wave. This is a symptom of the therapeutic effect of the drug, rather than its toxicity.

The emergence of a sinoatrial blockade or bifascicular blockade in the treatment of AV blockade of grade II or III requires withdrawal of the drug. The development of AV blockade of the I degree requires intensification of the patient's observation.

There have been reports of cases, sometimes lethal, of the appearance of a new arrhythmia or of an intensification of pre-existing and treated arrhythmia (see Section "Adverse Reactions").

The arrhythmogenic effect of amiodarone is weak or even lower such that it is observed in most antiarrhythmic drugs and usually manifests itself when certain combinations of drugs are used (see Section "Interaction with Other Drugs and Other Interactions") or in the presence of electrolyte imbalance. In spite of the fact that amiodarone can cause prolongation of QT interval, its ability to provoke paroxysmal ventricular torsades de pointes tachycardia is weak. During the treatment it is recommended to conduct an electrocardiogram.

From the side of the thyroid gland. This drug contains iodine, and therefore affects the results of certain indicators of thyroid function (binding of radioactive iodine, protein-bound iodine). But the definition of thyroid function indices (T3, T4, HF-TTG) can be fulfilled.

Amiodarone can cause thyroid dysfunction, especially in patients with a history of thyroid dysfunction. Quantitative determination of the TSH content is recommended for all patients before starting the use of the drug, then - regularly during treatment and for several months after drug discontinuation, as well as in case of clinical suspicion of thyroid dysfunction (see Section "Adverse Reactions").

From the side of the lungs. The appearance of dyspnoea or dry cough, both isolated and 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 pneumopathy and requires an x-ray examination of the patient (see Section "Adverse Reactions"). It is necessary to reconsider the advisability of using amiodarone, since interstitial pneumonitis, as a rule, is reversible in the early cancellation of amiodarone.

From the side of the liver. Regular monitoring of liver function is recommended at the beginning of the drug, then periodically during treatment with amiodarone (see Section "Adverse Reactions"). It is necessary to reduce the dose of amiodarone or to cancel this drug if the levels of transaminases grow more than three times as compared with the norm.When using amiodarone, acute hepatic disorders (including severe hepatocellular insufficiency or hepatic insufficiency, sometimes lethal) and chronic hepatic disorders can develop.

Neuromuscular disorders. Amiodarone can cause sensory, motor or mixed peripheral neuropathies and myopathies (see Section "Adverse Reactions").

From the side of the organs of sight. If there is blurred vision or reduced visual acuity, you should immediately perform a complete ophthalmological examination, including fundoscopy. The development of neuropathy or neuritis of the optic nerve caused by amiodarone requires withdrawal of the drug, as continued treatment can lead to progression of violations to blindness (see Section "Adverse Reactions").

Violations associated with interactions with other drugs. Combinations (see the section "Interaction with Other Drugs and Other Interactions") with such drugs as:

• beta-blockers, except sotalol (a combination is contraindicated) and esmolol (a combination that requires measures in the application);
• verapamil and diltiazem
• should be considered only for the prevention of life-threatening ventricular arrhythmias. Simultaneous use of amiodarone is not recommended with such drugs: beta-blockers, calcium channel blockers, which reduce the heart rate (verapamil, diltiazem), laxatives, which can lead to hypokalemia. Amiodarone is not recommended in combination with cyclosporin, diltiazem (for injection) and verapamil (for injection), some antiparasitic agents (halofantrine, lumefantrine and pentamidine), some neuroleptics (amisulpride, chlorpromazine, tsiamemazin, droperidol, fluphenazine, haloperidol, levomepromazine, pimozide , pipamperone, pipotiazine, sertindole, sulpiride, sultopride, tiapride, zuclopenthixol) and methadone (cm. 'interaction with other drugs and other types of interactions "section).

Disorders related to adjuvants. This drug contains lactose, so it is not recommended for use in patients intolerant of galactose, lactase deficiency or malabsorption of glucose and galactose (rare hereditary diseases).

Electrolyte disturbances, particularly hypokalemia. It is important to take into account the situations that may be associated with hypokalemia, which may contribute to the manifestation of proarrhythmic effects of the drug.

Hypokalemia must be removed prior to application of amiodarone.

The side effects listed below are most commonly associated with the excessive use of the drug, they can avoid or minimize the exact observance of the minimum maintenance dose.

Patients should be warned that during the treatment, they were not in the sun and use sunscreen.

Safety and efficacy of amiodarone children have not been evaluated in controlled clinical trials.

Because of the possible increase in the threshold defibrillation and / or stimulation of an implanted cardiac defibrillator or pacemaker must check this threshold before treatment with amiodarone and several times after the beginning of its application, and each time the correction of the dose.

Anesthesia. The anesthesiologist should be warned before the operation that the patient is taking amiodarone.

Long-term use may increase amiodarone haemodynamic risk associated with general or local anesthesia, and the risk of side effects, especially such as bradycardia, hypotension, reduction of cardiac output and impaired heart conduction. In addition, patients treated with amiodarone in the early postoperative period, there are several cases of acute respiratory distress syndrome. Therefore careful supervision is recommended for such patients under mechanical ventilation (see. Section "Adverse reactions").

The ability to influence the reaction rate when driving vehicles or other mechanisms

There are no data on the effect of the drug on the ability to drive or operate machinery there. However, the development of such side effects as a violation of the functions or disorders of the central nervous system, it is recommended to refrain from such activities.

Interaction with other drugs and other interactions

Antiarrhythmic drugs. Many antiarrhythmic drugs inhibit cardiac automaticity, conductivity and contractility of the myocardium.

The simultaneous use of antiarrhythmic agents belonging to different classes, can achieve favorable therapeutic effect, but often such a combination treatment is very delicate process that requires careful clinical and ECG monitoring. The simultaneous use of antiarrhythmic drugs that may induce the occurrence of torsades de pointes (such as amiodarone, disopyramide, quinidine compound, sotalol), contraindicated.

Concomitant use of antiarrhythmic drugs of the same class is not recommended, except in exceptional cases, since such treatment increases the risk of cardiac side effects.

Concomitant use with medicaments which have a negative inotropic effect, slows the heart rate and / or slows AV conduction, and therefore requires careful clinical and ECG monitoring.

Drugs that may induce the development of torsades de pointes. This arrhythmia can be induced by certain drugs, regardless of whether they relate to anti-arrhythmic drugs or not. Favorable factors are hypokalemia (see. Section "Drugs that decrease the potassium content"), bradycardia (see. Section "Formulations slowing heart rate") or congenital or acquired lengthening the interval QT.

The medicines that can cause the development of torsades de pointes, in particular, include antiarrhythmics Ia and III classes and some antipsychotics. For erythromycin, spiramycin and vinkamitsinu this interaction occurs only when used dosage forms which are administered by the intravenous route.

The simultaneous use of two drugs, each of which is a drug promoting emergence torsades de pointes, usually contraindicated.

However, methadone and some subgroups of drugs is an exception to this rule:

• antiparasitic drugs (halofantrine, lumefantrine, pentamidine) only is not recommended for use in conjunction with other agents that contribute to the appearance of torsades de pointes;
• antipsychotics, which may induce torsades de pointes, is also not recommended for use in conjunction with other agents that contribute to the emergence of torsades de pointes, but this combination is not contraindicated.

Drugs that slow the heart rate. Many drugs may be responsible for bradycardia. This particularly concerns the class Ia antiarrhythmic drugs , beta-blockers, certain antiarrhythmic drugs of class III, certain calcium channel blockers, digitalis drugs, pilocarpine and anticholinesterase drugs.

Combination is contraindicated (see Section:. "The Contra '). Drugs That may induce the occurrence of torsades de pointes of (The except antiparasitic drugs, neuroleptics and of methadone, see Section" Deprecated combination ".):

• Class Ia antiarrhythmics (quinidine, gidrohinidin, disopyramide)
• Class III antiarrhythmic drugs (dofetilide, ibutilide, sotalol)
• Other drugs, such as arsenic, bepridil, cisapride, difemanil, dolasetron (iv), erythromycin (iv), mizolastine, vinkamitsin (iv), moxifloxacin, spiramycin (a) toremifene.

Increased risk of ventricular arrhythmias, particularly torsades de pointes.

Of unauthorized combination.

Cyclosporine. Increased serum cyclosporine concentration due to the deterioration of its metabolism in the liver, the risk of manifestation nephrotoxic effects.

Quantitative determination of serum concentrations of cyclosporine, renal function monitoring and dose adjustment of cyclosporin treatment with amiodarone.

Fluoroquinolones. During treatment with amiodarone should be avoided fluoroquinolones .

Diltiazem injection. The risk of bradycardia and AV block.

If the use of this combination can not be avoided, it is essential to carry out a careful clinical monitoring and continuous ECG monitoring.

Verapamil injection. The risk of bradycardia and AV block.

If the use of this combination can not be avoided, it is essential to carry out a careful clinical monitoring and continuous ECG monitoring.

Antiparasitic drugs which can induce torsades de pointes (halofantrine, lumefantrine, pentamidine). Increased risk of ventricular arrhythmias, particularly torsades de pointes. If possible, you should cancel the 1 or 2 drugs. If the use of this combination can not be avoided, it is extremely important to perform preliminary evaluation of QT interval and perform EKG monitoring.

Neuroleptics, which can induce torsades de pointes (amisulpride, chlorpromazine, tsiamemazin, droperidol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperone, pipotiazine, sertindole, sulpiride, sultopride, tiapride, zuclopenthixol). Increased risk of ventricular arrhythmias, particularly torsades de pointes.

Methadone. Increased risk of ventricular arrhythmias, particularly torsades de pointes.

Combinations that require precautions for use.

Oral anticoagulants. Strengthening of the anticoagulant effect and increased risk of bleeding. Frequent monitoring of international normalizing ratio (MES). Possible adjustment of the dose of oral anticoagulant during treatment with amiodarone and within 8 days after discontinuation of the drug.

Beta-blockers other than sotalol (contraindicated combination) and esmolol (combination, which requires measures in the appendix). Violation of automatism and conductivity (inhibition of sympathetic compensatory mechanisms). ECG and clinical monitoring.

Beta-blockers, used for heart failure (bisoprolol, carvedilol, metoprolol, nebivolol). Violation of automaticity and conductivity infarction with the risk of excessive slowing of heart rate. Increased risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and a regular ECG monitoring.

Dabigatran. Increased plasma concentrations of dabigatran with an increased risk of bleeding events. Clinical monitoring and dose adjustment of dabigatran if necessary, but no higher than 150 mg / day.

Because amiodarone has a long half-life, the occurrence of interactions can be observed for several months after stopping treatment with amiodarone.

Substrates of P-glycoprotein. Amiodarone is an inhibitor of P-glycoprotein. It is expected that while the use of P-glycoprotein substrates will increase their concentration in the blood.

digitalis preparations. Inhibition of automaticity (excessive slowing of the heart rate) and violation AV-conduction.

In the application of digoxin observed increase in blood digoxin due to a decrease in clearance of digoxin.

ECG and clinical monitoring, quantitative determination of digoxin in blood and, if necessary, adjusting the dose of digoxin.

Diltiazem for oral administration. The risk of bradycardia or AV-blockade, especially in elderly patients. ECG and clinical monitoring.

Some macrolides (azithromycin, clarithromycin, roxithromycin). Increased risk of ventricular arrhythmias, particularly torsades de pointes.

ECG and clinical monitoring in particular the simultaneous use of these drugs.

Verapamil for oral administration. The risk of bradycardia and AV block, especially in elderly patients. ECG and clinical monitoring.

Esmolol. Violation contraction, automaticity and conduction (inhibition of sympathetic compensatory mechanisms). ECG and clinical monitoring.

Drugs that decrease the potassium content: diuretics reduce the potassium content (alone or in combination), stimulant laxatives, amphotericin B (intravenous), corticosteroids (for systemic use), tetracosactide. It is necessary to prevent the occurrence of hypokalemia (and the hypokalemia conduct correction) should be carefully control the duration of the interval QT. In case of paroxysmal ventricular tachycardia, torsades de pointes should not be used antiarrhythmics (ventricular pacing should start, possibly administration of magnesium preparations). Increased risk of ventricular arrhythmias, particularly torsades de pointes (hypokalaemia is a favorable factor). It is necessary to eliminate hypokalemia drug administration and exercise ECG monitoring,electrolyte content and clinical monitoring.

Lidocaine. The risk increases in plasma concentrations of lidocaine with possible cardiac and neurological side effects due to inhibition of amiodarone drug metabolism in the liver. The clinical and ECG-monitoring, and, if desired, quantitative determination of the plasma concentrations of lidocaine. If necessary - adjust dose of lidocaine during treatment with amiodarone and after its cancellation.

Orlistat. The risk reduction of plasma concentrations of amiodarone and its active metabolite. Clinical monitoring and, if necessary, ECG monitoring.

Phenytoin (by extrapolation - also fosphenytoin). Increased plasma concentrations of phenytoin with signs of overdose, particularly neurological signs (depression phenytoin metabolism in the liver). Clinical monitoring, quantification of plasma phenytoin concentrations and possible dosage adjustment.

Simvastatin. Increased risk of side effects (kontsentratsiezalezhne) such as rhabdomyolysis (depression simvastatin metabolism in the liver). Given this type of interaction should not exceed a dose of simvastatin 20 mg per day, or to apply other statin.

Tacrolimus. Increasing the concentration of tacrolimus in the blood due to the suppression of its metabolism by amiodarone. Quantitative determination of blood concentrations of tacrolimus, renal function monitoring and correction of the dose of tacrolimus in particular the simultaneous use of amiodarone and of its cancellation.

Drugs that slow the heart rate. Increased risk of ventricular arrhythmias, particularly torsades de pointes. The clinical and ECG monitoring.

Flecainide. Amiodarone increases plasma flecainide levels by inhibiting cytochrome SYR2D6. Therefore it is necessary to conduct correction dose flecainide.

Drugs metabolized by cytochrome R450ZA4. When such drugs are used simultaneously with amiodarone SYRZA4 inhibitor, it may increase their plasma levels and may lead to an increase in their toxicity.

Cyclosporine: combination with amiodarone may increase ciclosporin plasma levels. It is necessary to carry out the dose adjustment.
Fentanyl: combination with amiodarone may enhance the pharmacologic effects of fentanyl and increase the risk of toxicity.
Statins while the use of amiodarone and statins metabolized via SYRZA4 such as simvastatin, atorvastatin and lovastatin increases the risk of muscular toxicity. While the use of amiodarone is recommended to use statins are not metabolized via SYRZA4.
; Other drugs which are metabolized via SYRZA4: lidocaine, tacrolimus, sildenafil, midazolam, triazolam, dihydroergotamine, ergotamine, colchicine.
SYR2S9 substrates. Amiodarone increases the concentration of substances that are substrates SYR2S9 such as warfarin or phenytoin, by inhibiting cytochrome R4502S9.

Combinations which require special attention.

Pilocarpine. The risk of excessive slowing of heart rate (additive effects of drugs that slow the heart rate).

During treatment with amiodarone, it is recommended to avoid the use of CYPZA4 inhibitors (eg, grapefruit juice and certain medicines).

Pharmacological properties

Pharmacodynamics.

Antiarrhythmic properties.

The phase of the potential of cardiac cell action is extended mainly due to the slowing of the current in the potassium channels (class III according to Vaughan Williams classification).

It causes a bradycardic effect as a result of a decrease in the automatism of the sinus node. This action is not antagonistic atropine.

Has non-competitive alpha and beta anti-adrenergic effects.

Slows conduction in the sinoatrial node, atria and atrioventricular (AV) node, more pronounced with acceleration of the rhythm.

Does not change intraventricular conduction.

Increases the refractory period and reduces the excitability of the myocardium at the atrial, AV-node and ventricular levels.

Slows conduction and lengthens the refractory period in additional atrioventricular pathways.

Other properties.

Reduces oxygen consumption by myocardium due to a moderate decrease in peripheral resistance and a decrease in heart rate.

Increases coronary blood flow due to direct effects on the smooth muscle of the arteries of the myocardium and maintains cardiac output by lowering pressure and peripheral resistance, without revealing any negative inotropic effects.

A meta-analysis of the results of thirteen controlled randomized prospective clinical trials involving 6553 patients with recent myocardial infarction (78%) or chronic heart failure (22%) was performed.

The follow-up period for patients was 0.4 to 2.5 years. The average daily maintenance dose of amiodarone was 200 to 400 mg.

The meta-analysis showed a significant reduction in the overall mortality rate due to amiodarone, which was 13% (CI 95% 0.78-0.99, p = 0.030) and a 29% reduction in cardiac rhythm mortality (CI 95% 0, 59 -0.85, p = 0.0003).

However, the interpretation of these results should be approached cautiously, taking into account the heterogeneity of the studies, the results of which were included in the meta-analysis (the heterogeneity mainly concerns the selected patient population, the duration of the observation, the methodology for conducting and evaluating the results of the studies).

The percentage of patients who discontinued treatment was significantly higher in the group receiving amiodarone (41%) than in the placebo group (27%).

In 7% of patients receiving amiodarone, hypothyroidism occurred, compared with 1% in the placebo group.Hyperthyroidism was diagnosed in 1.4% of patients taking amiodarone and 0.5% of patients in the placebo group.

Interstitial pneumopathy was observed in 1.6% of patients taking amiodarone and 0.5% of patients in the placebo group.

Pharmacokinetics.

Amiodarone is a drug with a slow excretion and a pronounced affinity for the tissues.

Bioavailability after oral administration varies from 30% to 80% in different patients (mean 50%). After a single dose, the maximum concentration in the blood plasma is reached in 3-7 hours. Therapeutic effect is achieved on average within 1 week after starting the drug (from several days to two weeks).

The half-life of amiodarone is long, has a sufficiently high level of interindividual variability (from 20 to 100 days). During the first days of treatment, this drug accumulates in most body tissues, especially in adipose tissue. The conclusion starts in a few days, and the balance between admission and withdrawal is achieved within a few months with individual fluctuations.

Such characteristics explain the need for a loading dose to rapidly accumulate the drug in the body tissues, which is necessary to achieve a therapeutic effect.

Part of the iodine is released from the drug and is found in the urine in the form of iodide; 6 mg of iodine per day corresponds to a daily dose of amiodarone 200 mg. The rest of the drug, that is, most of the iodine is excreted with feces after metabolism in the liver.

Minor excretion of the drug with urine allows you to assign its usual doses to patients with impaired renal function.

After the withdrawal of treatment, excretion from the body continues for several months. It should be taken into account that after the withdrawal of the drug, its effect lasts from 10 days to 1 month.

Basic physical and chemical properties

Tablets of white or almost white color of flat-cylindrical form with a facet and a risk.

Shelf life

2 years.

Storage conditions

Store in a place inaccessible to children at a temperature not exceeding 25 ° C.

Packaging

For 10 tablets in a blister, 3 blisters per pack.

Category of leave

On prescription.