"Amiodarone": side effects, indications, dosage and instructions for admission

"Amiodarone" refers to a group of antiarrhythmic drugs. In modern medicine, it is considered one of the most effective drugs for the treatment of arrhythmia. The medicine is effective not only for preventive purposes, but also in cases where emergency care is required - with acute heart failure, myocardial infarction and in case of rhythm disturbance in patients in the intensive care unit. However, like other antiarrhythmic drugs, it has side effects. Amiodarone is increasingly prescribed by therapists and cardiologists. Along with this, the number of patients with complications due to the use of this drug is also increasing. Before using the medicine, it is recommended to take preventive measures that reduce the likelihood of developing negative manifestations.

pharmachologic effect

According to its pharmacological effects, Amiodarone 200 mg is one of the drugs used to interrupt and prevent angina attacks, which is the most common form of coronary heart disease. The medicine is also prescribed for other pathological conditions when coronary blood flow is disturbed.

The therapeutic effect is associated with the ability of the active substance to increase the duration of the oscillations of the membrane potential of the muscle cells of the heart, as well as change other parameters of this organ:

• the duration of the cardiac cycle, in which the myocardium is not excited (without this period, the pumping activity of the heart is impossible);
• the speed of the conducting signal in the atrioventricular node, which is the secondary center of cardiac stimulation;
• excitation of the bundle of His, a conducting system responsible for the transmission of a nerve impulse along the myocardium.

As a result, the automatism of the sinus node, which underlies arrhythmia, is reduced. This mechanism when using Amiodarone is associated with the following effects:

• blockade of potassium channels (decrease in the intensity of excretion of potassium ions from muscle cells of the heart);
• coronary expansion effect, decrease in the tone of the coronary vessels;
• reduced oxygen demand of the myocardium, increased energy reserves;
• inhibition of transmission of nerve impulses, a decrease in sensitivity to stimulation of the sympathetic nervous system;
• decrease in blood pressure (with intravenous administration).

Release form and composition

The drug is available in two forms: in the form of tablets, each of which contains 200 mg of the active compound - amiodarone hydrochloride, and in the form of a solution for injection (5% solution of 3 ml). The empirical formula of this chemical compound is C ₂₅ H ₃₀ ClI ₂ NO ₃ . The first form of release is most widely used in therapeutic practice. As can be seen from the chemical formula, the drug contains iodine, which affects the side effects of Amiodarone (violation of the thyroid gland).

The tablets are in blister packs of 10 pcs. Last 3 pcs. are placed in a cardboard box. Another option is also available - 30 tablets in glass jars in cardboard boxes.

Dosage and administration

Amiodarone is taken orally before meals. The tablets are washed down with water. The dosage of the drug is prescribed by the doctor in each case individually. The course of therapy should be carried out under the strict supervision of a medical professional.

In stationary conditions, the primary (loading) dose is usually 200-800 mg per day (400 mg on average). This number is divided into several doses per day. The maximum dosage of Amiodarone should not exceed 1.2 g per day and 400 mg once. The duration of a noticeable persistent effect in different patients has a very variable interval - from 2-3 days to 3 months. Accordingly, the total duration of treatment can be from 2-3 weeks to several months. With intravenous administration, the maximum concentration is detected after 1-30 minutes.

The maintenance dose for outpatient treatment varies between 100-400 mg per day. Amiodarone's side effects depend on the saturation of the active substance in the blood, therefore, the minimum necessary doses are prescribed for treatment (strictly according to the doctor’s instructions). To reduce the cumulative effect, a dosage regimen is also practiced in a day or within 2 days a week.

Pharmacokinetics

This drug is characterized by complex pharmacokinetics. This is due to the following factors:

• a very high degree of affinity for fats;
• a large volume of distribution in the human body;
• prolonged therapeutic effect;
• delayed action when taken orally;
• long period of elimination from the body.

The amount of the active substance of the tablets reaching the heart tissue ranges from 22-86% (on average, this value is 50%). When taken with food, bioavailability increases. The therapeutic concentration in the blood is 0.5-2.5 mg / ml. With a higher content of Amiodarone, side effects occur more often. After the cessation of treatment on the 3rd-10th day, its amount in the blood decreases by half. However, the true half-life (the time required to lose 50% of pharmacological activity) can reach 142 days. After taking the active substance is detected in the blood for up to 9 months.

The decomposition of Amiodarone 200 mg occurs in the liver. Metabolites (desethylamiodarone and others) are mainly excreted along with bile and feces, and only a small number of them are excreted through the kidneys with urine (up to 1% of the total dose). Absorption in the gastrointestinal tract, according to various estimates, is 20-55%. The active substance accumulates in fatty tissues and organs, which are characterized by a high level of blood supply (lungs, skin, spleen, liver), actively binding to proteins. When it is decomposed, iodine is also released, the amount of which can reach 80% of the concentration of the drug.

According to the instructions for use with Amiodarone 200 mg, the medicine is able to penetrate the placenta of a pregnant woman (up to half of the absorbed amount). The drug is also excreted in breast milk of the mother (up to a quarter of the dose).

Indications

This tool is used to treat the following pathologies:

• ventricular and supraventricular arrhythmia (including arrhythmia, accompanied by a serious condition that threatens the patient's life);
• tachycardia;
• prevention of atrial fibrillation, in which the atria are reduced at a frequency of 350-700 per minute;
• heart rhythm disturbances, in which immunity to conventional antiarrhythmic drugs is observed;
• angina pectoris;
• supraventricular and ventricular extrasystoles;
• arrhythmia, accompanied by coronary or chronic heart failure;
• parasystole - heart rhythm disturbance due to the presence of an additional focus of pulse generation;
• atrial fibrillation with Wolf-Parkinson-White syndrome;
• myocarditis in Chagas disease.

According to reviews, Amiodaron 200 in Russia is most often used to improve and maintain sinus rhythm. Abroad, in such cases, therapy is started with other drugs that are not registered in the Russian Federation (Ibutilide, Dofetilide). In Europe and the USA, this medicine is considered as an alternative, intended for patients with severe left ventricular myocardial hypertrophy and chronic heart failure.

This drug is also prescribed for the following groups of patients:

1. Elderly patients with severe exacerbation of atrial fibrillation.
2. Persons with suspected cardiac muscle damage due to tachycardia (for the prevention and control of arrhythmia).
3. Patients who have had myocardial infarction. Clinical studies show that the administration of a prophylactic dosage of Amiodarone for 12 months leads to a decrease in mortality among such patients.
4. Patients after heart surgery. In this category of people, supraventricular tachyarrhythmia occurs in 1/3 of cases after coronary artery bypass grafting, in half of cases after prosthetic heart valves and in 70% of patients after combined surgical interventions. Atrial fibrillation is a significant factor in mortality for such patients.

Contraindications

According to the instructions for use with Amiodarone 200 mg, the following contraindications exist for treatment with this drug:

• persistent reduction in the number of impulses of the sinus node (bradycardia);
• reduced concentration of potassium ions in blood plasma;
• weak sinus node syndrome, in which impulse transmission from the sinus node to the atria is impaired;
• CA- and AV-blockade above the 2nd degree;
• extreme degree of left ventricular failure, accompanied by a sharp decrease in the contractility of the heart muscle;
• hypertension;
• a sharp drop in blood pressure;
• thyroid pathology (long-term persistent lack of its hormones, thyrotoxicosis);
• chronic inflammatory diseases of the lung tissue;
• therapy with monoamine oxidase inhibitors (drugs prescribed for the treatment of chronic alcoholism and depression - Fenelzin, Pirlindol, Iproniazid, Isocarboxazide, Befol, Nialamide, Moclobemide, Tranylcypromine, Metralindol and others);
• period of pregnancy and lactation;
• hypersensitivity to iodine and other components of the drug.

With caution, it is prescribed in the following cases:

• with impaired liver function, its insufficiency;
• under the age of 18 years, since there is no clinical safety data in the treatment of children;
• with chronic heart and severe respiratory failure;
• in old age, since there is a high risk of severe bradycardia;
• with bronchial asthma.

Side effects and contraindications of "Amiodarone" are closely related to its pharmacokinetics and ability to accumulate in certain human organs. Patients taking this medicine are also advised to avoid direct rays of light. When the drug is discontinued, recurrence of arrhythmia may occur. The high iodine content (about 30% of the composition of the substance) and its metabolism influence the results of the radioactive test in the diagnosis of thyroid diseases.

Interaction with other drugs

This medication interacts with many other medicines. Lack of compatibility with Amiodarone is noted in the following products:

• antiarrhythmic drugs belonging to the classes of membrane-stabilizing blockers of sodium and potassium channels ("Quinidine", "Dofetilide", "Disopyramide", "Ibutilide", "Procainamide" and others);
• antipsychotics, phenothiazine and benzamide derivatives (Chlorpromazine, Levomepromazin, Flufenazin, Amisulpride and others);
• antipsychotic drugs, butyrophenones, Sertindol, Pimozide and others;
• macrolide antibiotics;
• Pentamidine (antiprotozoal agent);
• "Cisapride" and other laxatives, as they cause hypokalemia;
• azole antifungal drugs;
• anti-allergic drugs - "Astemizol", "Misolastine", "Terfenadine";
• fluoroquinolone antibiotics;
• calcium channel blockers (Bepridil, Naftidrofuril, Vinkamin and others);
• antimalarial drugs;
• other medicines - diphenyl methyl sulfate, beta-blockers, coumarins, Digoxin.

Concomitant use with the above medicines is undesirable, as this increases the risk of developing tachycardia (heart palpitations). According to reviews and instructions for Amiodarone, for many patients, such a large list of contraindications causes legitimate concerns. However, despite extensive limitations, this drug has unique effectiveness, which distinguishes it from other antiarrhythmic drugs.

"Amiodarone" is also prescribed with caution in combination with such means as:

• "Warfarin", "Procainamide", "Phenytoin", "Fosphenytoin" and "Digoxin", as their effect intensifies;
• systemic glucocorticosteroids;
• cardiac glycosides, since bradycardia is possible;
• photosensitizing drugs;
• immunosuppressants - Cyclosporin, Tacrolimus;
• analgesics - "Fentanyl", "Lidocaine";
• "Simvastatin" (used to reduce the concentration of "bad" cholesterol) - the risk of a toxic effect increases.

The effect of the tablets is reduced: the anti-allergic agent "Cimetidine", the drug for weight loss "Orlistat", grapefruit juice, the antibiotic "Rifampicin", as well as St. John's wort perforated. According to reviews to Amiodarone, side effects as a result of taking the above drugs can occur even several months after completion of treatment. This is due to its long term elimination from the human body.

Instructions for use "Amiodarone": side effects

The negative effects of taking the medicine are quite widespread. According to medical statistics, the following are most common among them:

• a change in the normal production of hormones in the thyroid gland, hypo- and hyperthyroidism - up to 10% of patients;
• inflammation of the mucous membrane of the esophagus, liver damage - 4-25% of patients;
• neurological abnormalities, headache, trembling in the extremities - 20-40%;
• amiodarone-induced pulmonary toxicity (AILT) - 5-17% of patients.

The last of the listed side effects of Amiodarone is the most dangerous, since in 5-20% of cases it leads to death. The forms and symptoms of this disease are described below.

Of the other possible complications that are noted in the instructions for "Amiodarone" 200 mg, the following:

• optic neuritis and neuropathy, accompanied by a decrease in visual function;
• the formation of lipid deposits in the cornea, manifested in the appearance of a halo or blurred contours of visual objects;
• dermatopathy - staining the skin in a gray-blue color, peeling, redness and inflammation, rash, depigmentation, hair loss, photosensitivity (excessive reaction to solar radiation);
• bradycardia (heart contractions less than 60 per minute);
• increased arrhythmia;
• tachycardia;
• increased signs of chronic heart failure;
• nausea, vomiting, metallic taste in the mouth, constipation, diarrhea, flatulence;
• toxic hepatitis, accompanied by jaundice, liver failure;
• a feeling of heaviness in the stomach;
• thrombocytopenia;
• syndrome of inadequate production of vasopressin, manifested in edema and a decrease in the daily volume of urine;
• disturbance of sleep, memory; delirium;
• inflammation of the epididymis, impotence;
• restriction of motor activity as a result of myopathy;
• impaired motor skills and coordination resulting from damage to the cerebellum;
• inflammation of the blood vessels;
• hemolytic anemia.

If these side effects and other symptoms occur, you must stop taking the drug, consult a doctor. In many cases, a reduction in the number of doses or a complete rejection of the drug leads to the reversibility of these changes in the patient's condition.

Overdose

If the dosage of Amiodarone tablets is exceeded, the following negative phenomena are recorded:

• falling heart rate;
• tachycardia;
• atrioventricular block from mild, manifested in bradycardia, to severe, when there is complete cardiac arrest;
• violation of the liver;
• chronic heart failure.

Treatment is with gastric lavage and symptomatic therapy.

Lung damage

AILT is one of the most serious complications arising from Amiodarone treatment. Side effects are manifested more often as a result of the presence of the following factors:

• pulmonary pathology in the patient's history;
• dosage over 400 mg / kg per day;
• long-term drug treatment;
• recently suffered damage to the lung tissue (various injuries, hemorrhage, embolism, and others);
• conducting oxygen therapy, artificial respiration after surgery.

The causes of death in unrecognized inflammation of the lung tissue are often mistaken for heart disease. There are several forms of AILT:

• ARDS (acute respiratory distress syndrome or non-cardiogenic pulmonary edema);
• obliterating bronchiolitis, complicated by pneumonia (inflammatory obstruction or impaired airway);
• pulmonary fibrosis (replacement of the functional tissue of this organ with fibrous, as a result of which there is a violation of its elasticity and gas exchange in the body).

The mechanisms of toxic lung damage with the use of Amiodarone in medical science have not yet been fully investigated. The active substance of this drug has both a direct (due to a cytotoxic effect) and an indirect damaging effect on lung cells. Most often, this complication manifests itself in the first months of treatment. It can also develop within 2 days after the first dose. The greatest risk of detecting AILT at a dosage of 400 mg / day.- 2 months after the start of treatment, and at 200 mg / day. - after 2 years.

After its cancellation, 60% of patients have reversible changes in a positive direction, however, the prognosis is favorable only with an early diagnosis. Such patients are prescribed analogues of Amiodarone.

Symptoms of AILT, diagnosis and treatment

Damage to the lungs when taking this drug is accompanied by the following symptoms:

• dyspnea;
• chest pain;
• wheezing in the lungs;
• temperature rise;
• cough;
• weight loss;
• weakness.

These signs are not specific and are often perceived by patients as ARI or a manifestation of heart failure. This approach makes it difficult to correctly diagnose, increases the risk of death.

The following methods are used as instrumental methods for determining the disease:

1. X-ray of the lungs. The image shows infiltrates. Most often, the right lung is affected, in particular its upper lobe.
2. Computed tomography of the lungs. Found dimming type "frosted glass", high density infiltrates and tumor-like shadows in the form of nodules, foci, thickening of the pleura, fluid accumulation in the pleural region. Infiltrates can be either single or multiple. In most cases, they are located in the marginal regions of the lungs.
3. General and biochemical analysis of blood. An increase in the level of lactate dehydrogenase, mucin-like glycoprotein, leukocytes, eosinophils is detected.

AILT can develop within a few days after the start of Amiodarone therapy. Risk factors for its occurrence are also harmful working conditions and smoking.

If the above symptoms appear, you need to see a doctor and conduct an additional examination. In advanced cases, pneumofibrosis develops with severe oxygen and respiratory failure, and hypoxemic coma occurs. By agreement with the doctor, taking Amiodarone is discontinued. If there is a need, then drugs with a different chemical composition (“Propafenone”, “Sotalol Canon” and others) that are similar in effect are prescribed.

AILT is treated with systemic glucocorticosteroids, Prednisolone. Therapy should last 4-12 months. Its premature termination can lead to a new relapse (especially in obese people), since Amiodarone tends to accumulate in the tissues of the body and has a long half-life. In severe cases, patients are prescribed extracorporeal oxygenation - artificial hardware oxygen saturation of the blood. Animal experiments have shown that the negative effects of AILT also reduce the intake of vitamin E, however, such studies have not been conducted in humans.

Thyroid disease

Side effects associated with disruption of the thyroid gland are most often observed in those patients who already had dysfunction of this organ before taking Amiodarone. 10% of the iodine contained in the preparation is in a free state. Associated iodine also affects hormone metabolism. As a result, the following deviations may develop:

• hypothyroidism (persistent lack of thyroid hormones);
• hyperthyroidism (an excess of its hormones);
• thyrotoxicosis (intoxication with thyroid hormones).

The second condition often leads to atrial fibrillation, tachycardia and increased arrhythmia. If the above pathologies are identified, the reception of Amiodarone should be discontinued. Abnormal changes in the thyroid gland to varying degrees are found in half of the patients taking this drug.

Treatment of thyrotoxicosis is carried out using glucocorticoids, "Tiamazole", potassium perchlorate. In severe cases, patients are removed from the thyroid gland.

Prevention of Complications

Before using Amiodarone tablets, additional examinations should be prescribed to the patient:

• X-ray of the lungs
• assessment of the function of external respiration (HFD);
• X-ray examination of the thyroid gland.

If long-term administration of the drug is planned, then it is necessary to regularly check the function of the thyroid gland, lungs, and undergo examinations by an ophthalmologist. Patients belonging to the category of persons at high risk of complications should be examined at least 1 time in 3 months, the rest - 1 time per year. These measures make it possible to detect AILT and thyroid dysfunction at an early stage, as well as conduct timely treatment.

Patient Reviews

Reviews from the use of "Amiodarone" are mostly positive. Most often, it is prescribed for older people suffering from ventricular fibrillation, arrhythmia. The medicine effectively helps even with large jumps in blood pressure. Taking the drug makes it possible to significantly improve the quality of life of patients, avoid paroxysms and emergency resuscitation.

Among the most common side effects, patients note digestive disorders (vomiting), shortness of breath, thyrotoxicosis and neurological abnormalities. With the intensification of such phenomena, in consultation with the doctor, you can switch to another treatment regimen with longer breaks. This contributes to better tolerance of the drug.

Analogs

Direct analogues in composition and indication for this drug are Cordaron, Rotaritmil, Amiocordin and Cardiodarone. The properties of these drugs vary slightly. "Cordaron" is produced in European countries from higher quality raw materials. Accordingly, the price of this medicine is higher than that of Amiodarone. However, cheaper generics have the property of high variability of the concentration of the active substance in the blood plasma than the original drugs.

According to reviews on Amiodarone analogues received from doctors and patients, replacing the original with identical equivalents of this drug leads to an increase in the number of recurrences of arrhythmia. This phenomenon is observed in half of all cases. Therefore, it is not recommended to change antiarrhythmic drugs, especially with their long-term use. This is especially true for those patients who have arrhythmia in a life-threatening form, as well as accompanied by loss of consciousness.