Sedacoron^® (Tablets, Concentrate) Instructions for Use

ATC Code

C01BD01 (Amiodarone)

Active Substance

Amiodarone (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antiarrhythmic drug

Pharmacotherapeutic Group

Antiarrhythmic agent

Pharmacological Action

Class III antiarrhythmic agent, possesses antianginal action.

The antiarrhythmic effect is associated with the ability to increase the duration of the action potential of cardiomyocytes and the effective refractory period of the atria, ventricles of the heart, AV node, bundle of His, and Purkinje fibers. This is accompanied by a decrease in the automaticity of the sinus node, slowing of AV conduction, and a decrease in the excitability of cardiomyocytes. It is believed that the mechanism of increasing the duration of the action potential is associated with the blockade of potassium channels (reducing the efflux of potassium ions from cardiomyocytes). By blocking inactivated “fast” sodium channels, it exerts effects characteristic of Class I antiarrhythmic agents. It inhibits the slow (diastolic) depolarization of the sinus node cell membrane, causing bradycardia, and suppresses AV conduction (an effect of Class IV antiarrhythmics).

The antianginal effect is due to coronary vasodilating and antiadrenergic action, reducing myocardial oxygen demand. It exerts an inhibitory effect on α- and β-adrenergic receptors of the cardiovascular system (without their complete blockade). Reduces sensitivity to hyperstimulation of the sympathetic nervous system, tone of coronary vessels; increases coronary blood flow; reduces heart rate; increases the energy reserves of the myocardium (by increasing the content of creatine sulfate, adenosine, and glycogen). Reduces total peripheral vascular resistance and systemic blood pressure (with intravenous administration).

It is believed that Amiodarone may increase the level of phospholipids in tissues.

It contains iodine. Affects the metabolism of thyroid hormones, inhibits the conversion of T₃ to T₄ (blockade of thyroxine-5-deiodinase) and blocks the uptake of these hormones by cardiocytes and hepatocytes, which leads to a weakening of the stimulating effect of thyroid hormones on the myocardium (T₃ deficiency can lead to its overproduction and thyrotoxicosis).

When taken orally, the onset of action is from 2-3 days to 2-3 months, the duration of action is also variable – from several weeks to several months.

After intravenous administration, the maximum effect is achieved in 1-30 minutes and lasts 1-3 hours.

Pharmacokinetics

After oral administration, it is slowly absorbed from the gastrointestinal tract, absorption is 20-55%. C_max in blood plasma is reached in 3-7 hours.

Due to intensive accumulation in adipose tissue and organs with high blood supply (liver, lungs, spleen), it has a large and variable V_d and is characterized by a slow achievement of equilibrium and therapeutic concentration in blood plasma and prolonged elimination. Amiodarone is detected in blood plasma for up to 9 months after discontinuation of its use. Protein binding is high – 96% (62% with albumin, 33.5% with β-lipoproteins).

Penetrates the blood-brain barrier and placental barrier (10-50%), is excreted in breast milk (25% of the dose received by the mother).

Extensively metabolized in the liver to form the active metabolite desethylamiodarone, and also, apparently, by deiodination. With prolonged treatment, iodine concentrations can reach 60-80% of the amiodarone concentration. It is an inhibitor of the liver isoenzymes CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP3A7.

Elimination is biphasic. After oral administration, T_1/2 in the initial phase is 4-21 days, in the terminal phase – 25-110 days; for desethylamiodarone – on average 61 days. Typically, with course oral administration, the T_1/2 of amiodarone is 14-59 days. After intravenous administration of amiodarone, T_1/2 in the terminal phase is 4-10 days. It is excreted mainly with bile through the intestines, and slight enterohepatic recirculation may be observed. In very small amounts, Amiodarone and desethylamiodarone are excreted in the urine.

Amiodarone and its metabolites are not removed by dialysis.

Indications

Treatment and prevention of paroxysmal rhythm disorders: life-threatening ventricular arrhythmias (including ventricular tachycardia), prevention of ventricular fibrillation (including after cardioversion), supraventricular arrhythmias (usually when other therapy is ineffective or impossible, especially those associated with WPW syndrome), including paroxysms of atrial fibrillation and flutter; atrial and ventricular extrasystole; arrhythmias against the background of coronary insufficiency or chronic heart failure, parasystole, ventricular arrhythmias in patients with Chagas myocarditis; angina pectoris.

ICD codes

Dosage Regimen

For oral administration in adults, initiate therapy with a loading dose to achieve a rapid therapeutic effect. Administer 600 mg to 1200 mg daily, divided into two or three doses, for 7 to 14 days.

Following the loading phase, gradually reduce the dosage to a maintenance dose. The typical maintenance dose ranges from 200 mg to 400 mg daily. In some cases, the lowest effective dose, such as 200 mg every other day or 100 mg daily, may be sufficient for long-term control.

For intravenous infusion in a hospital setting, administer a loading infusion of 5 mg/kg in 250 mL of 5% glucose solution over 20 minutes to 2 hours. This can be followed by a continuous maintenance infusion at a rate of 10 to 20 mg/kg over 24 hours, up to a maximum daily dose of 1.2 grams.

Transition from intravenous to oral therapy by initiating the oral loading dose concurrently with the final 24-hour intravenous infusion.

For pediatric patients, the dose is 2.5 mg/kg to 10 mg/kg per day. Adjust the dosage and administration interval based on clinical response and tolerance.

Due to the drug’s extremely long half-life and risk of accumulation, titrate the maintenance dose to the lowest effective level. Regularly re-evaluate the need for continued therapy. Monitor for efficacy and adverse effects closely during dose adjustments.

Adverse Reactions

From the cardiovascular system sinus bradycardia (refractory to m-cholinoblockers), AV block, with prolonged use – progression of CHF, torsades de pointes ventricular arrhythmia, exacerbation of existing arrhythmia or its occurrence, with parenteral use – decrease in blood pressure.

From the endocrine system development of hypo- or hyperthyroidism.

From the respiratory system with prolonged use – cough, shortness of breath, interstitial pneumonia or alveolitis, pulmonary fibrosis, pleurisy, with parenteral use – bronchospasm, apnea (in patients with severe respiratory failure).

From the digestive system nausea, vomiting, decreased appetite, dulling or loss of taste, feeling of heaviness in the epigastrium, abdominal pain, constipation, flatulence, diarrhea; rarely – increased activity of liver transaminases, with prolonged use – toxic hepatitis, cholestasis, jaundice, liver cirrhosis.

From the nervous system headache, weakness, dizziness, depression, feeling of fatigue, paresthesia, auditory hallucinations, with prolonged use – peripheral neuropathy, tremor, memory impairment, sleep disorders, extrapyramidal manifestations, ataxia, optic neuritis, with parenteral use – intracranial hypertension.

From the sense organs: uveitis, deposition of lipofuscin in the corneal epithelium (if the deposits are significant and partially fill the pupil – complaints of luminous spots or a veil before the eyes in bright light), microdetachment of the retina.

From the hematopoietic system thrombocytopenia, hemolytic and aplastic anemia.

Dermatological reactions skin rash, exfoliative dermatitis, photosensitivity, alopecia; rarely – gray-blue discoloration of the skin.

Injuries, intoxications and procedural complications frequency unknown – primary graft dysfunction after heart transplantation.

Local reactions thrombophlebitis.

Other epididymitis, myopathy, decreased potency, vasculitis, with parenteral use – fever, increased sweating.

Contraindications

Sinus bradycardia, sick sinus syndrome, sinoatrial block, AV block II-III degree (without the use of a pacemaker), cardiogenic shock, hypokalemia, collapse, arterial hypotension, hypothyroidism, thyrotoxicosis, interstitial lung diseases, use of MAO inhibitors, pregnancy, lactation period, hypersensitivity to amiodarone and to iodine.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation.

Amiodarone and desmethylamiodarone cross the placental barrier, their concentrations in fetal blood are 10% and 25% of the concentration in maternal blood, respectively.

Amiodarone and desmethylamiodarone are excreted in breast milk.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Pediatric Use

Use with caution under the age of 18 years (efficacy and safety of use have not been established).

Geriatric Use

Use with caution in elderly patients (high risk of developing severe bradycardia).

Special Precautions

Use with caution in chronic heart failure, hepatic insufficiency, bronchial asthma, in elderly patients (high risk of developing severe bradycardia), under the age of 18 years (efficacy and safety of use have not been established).

Should not be used in patients with severe respiratory failure.

According to retrospective studies, the use of amiodarone before heart transplantation increases the risk of primary graft dysfunction, in which dysfunction of the left, right, or both ventricles occurs within 24 hours after transplantation. Severe primary graft dysfunction may be irreversible. It should also be noted that patients on the transplant waiting list should switch to alternative treatment options as early as possible.

Before starting amiodarone, a chest X-ray and thyroid function tests should be performed, and, if necessary, electrolyte disturbances should be corrected.

With long-term treatment, regular monitoring of thyroid function, consultations with an ophthalmologist, and chest X-ray are necessary.

Parenterally, it can only be used in specialized hospital departments under constant monitoring of blood pressure, heart rate, and ECG.

Patients receiving Amiodarone should avoid direct exposure to sunlight.

When amiodarone is discontinued, recurrences of cardiac arrhythmias are possible.

May affect the results of the radioactive iodine uptake test by the thyroid gland.

Amiodarone should not be used simultaneously with quinidine, beta-blockers, calcium channel blockers, digoxin, coumarin, doxepin.

Drug Interactions

Drug interaction of amiodarone with other drugs is possible even several months after its discontinuation due to its long T_1/2.

With simultaneous use of amiodarone and Class I A antiarrhythmic agents (including disopyramide), the QT interval increases due to an additive effect on its value and the risk of developing torsades de pointes ventricular tachycardia increases.

With simultaneous use of amiodarone with laxatives that can cause hypokalemia, the risk of developing ventricular arrhythmia increases.

Agents causing hypokalemia, including diuretics, corticosteroids, amphotericin B (IV), tetracosactide, when used simultaneously with amiodarone, cause an increase in the QT interval and an increased risk of ventricular arrhythmia (including torsades de pointes).

With simultaneous use of agents for general anesthesia, oxygen therapy, there is a risk of developing bradycardia, arterial hypotension, conduction disorders, and a decrease in cardiac output, which is apparently due to additive cardiodepressive and vasodilating effects.

With simultaneous use, tricyclic antidepressants, phenothiazines, astemizole, terfenadine cause an increase in the QT interval and an increased risk of ventricular arrhythmia, especially torsades de pointes.

With simultaneous use of warfarin, phenprocoumon, acenocoumarol, the anticoagulant effect is enhanced and the risk of bleeding increases.

With simultaneous use of vincamine, sultopride, erythromycin (IV), pentamidine (IV, IM), the risk of developing torsades de pointes ventricular arrhythmia increases.

With simultaneous use, an increase in the plasma concentration of dextromethorphan is possible due to a decrease in the rate of its metabolism in the liver, which is caused by inhibition of the activity of the CYP2D6 isoenzyme of the cytochrome P450 system under the influence of amiodarone and a slowdown in the elimination of dextromethorphan from the body.

With simultaneous use of digoxin, the plasma concentration of digoxin significantly increases due to a decrease in its clearance and, as a result, the risk of digitalis intoxication increases.

With simultaneous use of diltiazem, verapamil, negative inotropic effect, bradycardia, conduction disturbance, AV block are enhanced.

A case of increased plasma concentration of amiodarone during its simultaneous use with indinavir has been described. It is believed that ritonavir, nelfinavir, saquinavir will have a similar effect.

With simultaneous use of cholestyramine, the plasma concentration of amiodarone decreases due to its binding to cholestyramine and reduced absorption from the gastrointestinal tract.

There are reports of an increase in the plasma concentration of lidocaine during simultaneous use with amiodarone and the development of seizures, apparently due to inhibition of lidocaine metabolism under the influence of amiodarone.

It is believed that synergism is possible regarding the inhibitory effect on the sinus node.

With simultaneous use of lithium carbonate, hypothyroidism may develop.

With simultaneous use of procainamide, the QT interval increases due to an additive effect on its value and the risk of developing torsades de pointes ventricular tachycardia. Increase in plasma concentration of procainamide and its metabolite N-acetylprocainamide and enhancement of side effects.

With simultaneous use of propranolol, metoprolol, sotalol, arterial hypotension, bradycardia, ventricular fibrillation, asystole are possible.

With simultaneous use of trazodone, a case of torsades de pointes arrhythmia has been described.

With simultaneous use of quinidine, the QT interval increases due to an additive effect on its value and the risk of developing torsades de pointes ventricular tachycardia. Increase in plasma concentration of quinidine and enhancement of its side effects.

With simultaneous use, a case of enhancement of the side effects of clonazepam has been described, which is apparently due to its accumulation as a result of inhibition of oxidative metabolism in the liver under the influence of amiodarone.

With simultaneous use of cisapride, the QT interval significantly increases due to an additive effect, risk of developing ventricular arrhythmia (including torsades de pointes).

With simultaneous use, the plasma concentration of cyclosporine increases, risk of developing nephrotoxicity.

A case of pulmonary toxicity has been described with simultaneous use of high-dose cyclophosphamide and amiodarone.

The plasma concentration of amiodarone increases due to slowing of its metabolism under the influence of cimetidine and other inhibitors of liver microsomal enzymes.

It is believed that due to inhibition by amiodarone of liver enzymes involved in the metabolism of phenytoin, an increase in the plasma concentration of the latter and an enhancement of its side effects are possible.

Due to induction of liver microsomal enzymes under the influence of phenytoin, the rate of metabolism of amiodarone in the liver increases and its plasma concentration decreases.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.