The drug is used when it is necessary to get a quick action of the drug or if oral treatment is impossible. Treatment of severe cardiac arrhythmias such as supraventricular arrhythmias with rapid ventricular function, tachycardia associated with pre-excitation syndrome (Wolff-Parkinson-White syndrome) and diagnosed symptomatic ventricular rhythm disturbances.
Class III anti-arrhythmic drug. It strongly blocks potassium channels, slightly blocks high-speed sodium channels and Calcium channels, and moderately blocks α and β adrenergic receptors. The antiarrhythmic action of amiodarone consists in: elongation of phase 3 of action potential, reduction of sinus node automatism, non-competitive inhibition of α- and β-adrenergic receptors, release of atrial, vestibular and nodal conduction, prolongation of refraction and reduction of myocardial excitability at the level of atria, node and chambers, releasing the conduction of the impulse and prolonging the refractory period of an additional vestibular pathway. Haemodynamics and prevention of ischemia include moderate peripheral resistance reduction and decreased heart rate (leading to reduced oxygen consumption in the myocardium), non-competitive inhibition of α- and β-adrenergic receptor activation, increased coronary artery blood flow, maintenance of ejection volume. Intravenous administration causes hypotension, which results from the reduction of vascular resistance and negative inotropic effect. Serious hypotension can be prevented by reducing the infusion rate. After intravenous injection, amiodarone rapidly reaches the maximum serum concentration. In myocardium, the maximum concentration occurs already after a few minutes after intravenous injection; the concentration in the myocardium is higher than in the plasma. It is metabolised mainly in the liver, partly also in the gut (ie in the intestinal mucosa). In the liver, it is metabolised by CYP3A4. Major metabolic pathways include processes such as dehydrogenation, hydroxylation, O- and N-dealkylation (deethylation). The N-deethylation process produces deethylamiodaron, the main pharmacologically active metabolite of amiodarone. Amiodarone is secreted in the bile (in the stool) and through the kidneys. T0,5 after a single intravenous injection, it is on average 3.2-20.7 h; after prolonged administration of T0,5 it is very long, ie 13-103 days (average 53 ± 24 days). During the first few days of treatment, amiodarone accumulates in the body. Elimination begins after a few days. The steady plasma concentration is reached gradually over several weeks or months. After discontinuation, elimination of amiodarone lasts for several months.
Contraindications:
Hypersensitivity to amiodarone or to any of the excipients. Sinus bradycardia or sinoatrial block. Disorders of sinus node function (if the patient has no pacemaker). Atrioventricular block, two- or three-beam leg block in patients without a pacemaker. Circulatory collapse. Severe hypotension. Concurrent use of drugs that may induce multiform ventricular tachycardiatorsade de pointes. Thyroid disease. Pregnancy (except for the most urgent cases where the anticipated effect justifies the risk) and breastfeeding. Contraindications to intravenous injections also include severe respiratory failure, decompensated cardiomyopathy and severe heart failure. Due to the content of benzyl alcohol, the preparation is contraindicated in neonates, infants and children up to 3 years of age.
Precautions:
Treatment with the solution for injection takes place only in intensive care units. In general, intravenous injections are not recommended due to possible hemodynamic disorders (severe hypotension, circulatory insufficiency). Injections can only be used in cases of emergency when substitution therapy has failed.If possible, the solution for injection should be administered by intravenous infusion. Hypotension, bradycardia and AV block may occur during the infusion; therefore, the infusion rate should be closely monitored and the instructions for administration should be followed exactly. Special care should be taken in patients with hypotension, respiratory failure, cardiomyopathy or heart failure. Due to the possibility of venous inflammation during treatment, administration of the infusion through the central venous catheter is recommended. Before starting treatment, electrocardiography, thyroid function tests and determination of serum potassium should be performed. The pharmacological action of amiodarone may cause ECG changes: prolongation of the QT interval (due to prolonged repolarization period) and formation of U wave - this type of lesion is not a sign of heart toxicity. If the sinoatrial block occurs, AV block IIst. or IIIst. or the double beam beam, treatment should be discontinued. Growing dyspnoea and a dry cough may indicate a toxic effect of amiodarone on the lungs. The drug may cause thyroid dysfunction, especially in patients with a history of personal or family thyroid. Due to the risk of acute respiratory distress syndrome, close monitoring of the patient and supervision of oxygen concentration in the respiratory gases (FiO2) as well as oxygen saturation indicators (SaO2, PaO2) are recommended after surgery. Serum liver enzymes, in particular transaminases, should be monitored regularly during treatment. Special care should be taken in elderly patients (the smallest loading and maintenance doses are recommended). The safety and efficacy of amiodarone in children have not been established.
Pregnancy and lactation:
There are no adequate data on the use of the drug during pregnancy. Due to the effect on the fetal thyroid, amiodarone is contraindicated in pregnancy, except in special situations. Amiodarone is excreted in large amounts in milk - do not use during breastfeeding.
Side effects:
Common: severe bradycardia, hypotension (severe hypotension or collapse may occur after an overdose or following a too rapid injection), phlebitis after intravenous infusion (which can be avoided by using a central venous catheter). Very rare: anaphylactic shock, mild intracranial hypertension, headache, excessive sweating, moderate bradycardia, sinus node retention (requiring discontinuation of Amiodarone, especially in patients with impaired conduction of excitation and / or elderly), exacerbation of existing or a new arrhythmia (sometimes followed by cardiac arrest), hot flushes, interstitial pneumonitis, acute respiratory distress syndrome, bronchospasm and / or apnea in patients with severe respiratory disease (especially in patients with asthma), nausea, elevation serum transaminases (usually moderate 1.5-3-fold above the norm, after dose reduction may return spontaneously), severe abnormal liver function with high transaminase levels and / or jaundice (sometimes fatal) - in such cases should be discontinued administration of the drug.
Dosage:
Intravenous injection: usually 5 mg / kg, administered for at least 3 minutes. Do not give another intravenous injection before at least 15 minutes. after the first administration, even if the content of one ampoule is given (due to the risk of irreversible collapse). The therapeutic effect occurs in the first minutes and then gradually decreases. The use of the infusion allows for maintaining the action of the drug.Intravenous infusion: usually initially (loading dose) 5 mg / kg in 250 ml of 5% Glucose for a period of 20 minutes to 2 hours. The infusion rate should be adjusted to the effect of action. The dose may be repeated 2 to 3 times in 24 hours. The maximum daily dose of 1200 mg should not be exceeded. The maintenance dose is 10 to 20 mg / kg per day (usually 600 to 800 mg per day, but not more than 1200 mg), given in 250 ml of 5% glucose. Treatment with an infusion usually lasts 4 to 5 days. Oral treatment should start on the first day of treatment with an infusion.