Amiodarone - instructions for use, doses, side effects, contraindications

Influencing the lipid environment of ion channels, comparatively briefly blocks inactivated fast sodium channels,reduces calcium current, short-time outgoing current, potassium currents of abnormal and delayed rectification; non-competitive adrenoblocking activity; disturbance of conduction through intercellular contacts.

Pharmacological effects

Antiarrhythmic: an increase in the duration of the action potential and the refractory period in all tissues of the heart without a significant effect on the membrane potential.

The onset of action is from 2-3 days to 2-3 months (even against the background of loading doses).

Decrease in the automatism of the CA node, prolongation of the atrioventricular conduction, decrease in the automaticity of spontaneous excitation in the Purkinje filament system, slowing down of the conduction along additional conductive paths (WPW syndrome).

Antianginal. ECG: decrease in heart rate, lengthening of intervals P-Q, Q-T, possibly moderate expansion of QRS complex. Blockade of thyroxine-5-deiodinase (transformation of T4 into T3) and capture of hormones by cardiomyocytes and hepatocytes (weakening of the stimulating effect of thyroid hormones on the myocardium).

Pharmacokinetics:

F is 40-50%. VD - 66 ± 44 l / kg. The connection with plasma proteins is 99.9%. Biotransformation in the liver with the formation of an active metabolite - desethylamiodarone (CYP3A3 / 4, CYP3A5, CYP3A7). T1 / 2 ~ 40-55 days, desethylamiodarone ~ 61 days.Cl - 1.9 ± 0.4 ml / min / kg. Elimination with feces. Penetrates through the BBB, placenta. It is not excreted by hemodialysis.

Indications:

Treatment and prevention of paroxysmal rhythm disturbances: life-threatening ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation) - increases hospital survival in patients with paroxysms of ventricular fibrillation, supraventricular arrhythmias (usually with ineffectiveness or impossibility of other therapies, especially those associated with WPW syndrome), in including paroxysmal form of atrial fibrillation and flutter, ventricular arrhythmias in patients with Chagas myocarditis.

Atrial and ventricular extrasystole.

Arrhythmias on a background of coronary or heart failure - reduces the risk of fatal outcome. Parasystole. Ventricular arrhythmias in patients with Chagas myocarditis.

Preventing atrial fibrillation after heart surgery.

Decrease in ventricular rhythm in patients with refractory ciliary tachyarrhythmia (in combination with digoxin and / or β-adrenoblockers). Ventricular and supraventricular arrhythmias (therapy is initiated in a medical institution or under the supervision of a specialist).

Ventricular fibrillation or ventricular tachycardia without pulse.

ICD-10

IX.I30-I52.I45.6 Syndrome of premature agitation

IX.I30-I52.I47.1 Nadzheludochkovaya tachycardia

IX.I30-I52.I47.2 Ventricular tachycardia

IX.I30-I52.I48 Atrial fibrillation and flutter

IX.I30-I52.I49.0 Fibrillation and flutter of the ventricles

IX.I30-I52.I49.4 Other and unspecified depolarization

Contraindications:

Hypersensitivity (including iodine), SSSU, sinus bradycardia, sinoatrial blockade, AV blockade of II-III degree (without use of pacemaker), cardiogenic shock, hypokalemia, collapse, arterial hypotension, hypothyroidism, thyrotoxicosis, interstitial lung diseases, inhibitors MAO, pregnancy, breast-feeding.

Carefully:

CHF, thyroid disease, hepatic insufficiency, bronchial asthma, pregnancy, advanced age (high risk of severe bradycardia), age to 18 years (efficacy and safety of use not established).

Pregnancy and lactation:

FDA recommendations in Category D. Adequate and well-controlled studies in humans have not been conducted. Amiodarone Inward during pregnancy should be used only if the benefit to the mother outweighs the unknown risk to the fetus.It is necessary to inform about the risk for the fetus of patients taking amiodarone during pregnancy or becoming pregnant while taking this medication. Amiodarone penetrates the placenta.

Dosing and Administration:

Average therapeutic single dose 0.2 g, daily dose 0.4 g, maximum single dose 0.4 g, maximum daily dose 0.8 g (up to 1.2 g). Inside (before eating) 0.6 g in 3 doses, after 5-15 days the dose is reduced to 0.3-0.4 g / day, then go on maintenance therapy at 0.2-0.3 g / day in 2 reception. To avoid cumulation take for 5 days, then break 2 days; or 3 weeks per month with a weekly break.

For relief of acute rhythm disturbances, IV is administered at the rate of 5 mg / kg, patients with heart failure 2.5 mg / kg. Short-term infusions are carried out for 10-20 minutes in 40 ml of 5% dextrose solution; if necessary, repeated infusion after 24 hours. For long infusions, 0.6-1.2 g / day in 500-1000 ml of 5% dextrose solution or in 0.9% solution of sodium chloride at the rate of 150 mg per 250 ml of solution.

Use in children

Ventricular and supraventricular arrhythmias (therapy is initiated in a medical institution or under the supervision of a specialist).

Inside. Newborns: starting from 5 mg / kg 2-3 times a day for 7-14 days, then the dose is reduced to a maintenance dose of 5 mg / kg per day.1 month to 12 years: from 5-6.5 mg / kg (maximum 200 mg) 2-3 times a day (or 500 mg / m2 per day) for 7-10 days, then reduce the dose to 5-10 mg / kg once a day (or 250 mg / m2 per day); maximum 200 mg / day. 12-18 years: 200 mg three times a day for 7 days, then 200 mg twice a day for 7 days, then a maintenance dose of 200 mg / day or a minimum effective dose.

Ventricular fibrillation or ventricular tachycardia without pulse.

In / in the infusion. Newborns: starting at 5 mg / kg for 30 minutes, then 5 mg / kg for 30 minutes every 12-24 hours 1 month to 18 years: starting at 5 mg / kg for 20-120 minutes, then at a continuous infusion at a rate of 300-900 μg / kg per hour; maximum 1.2 g every 24 hours. It is best to enter the central vein under ECG monitoring in the intensive care unit. Dilute in a solution of 5% dextrose in a concentration of at least 600 μg / ml.

Not compatible with sodium chloride solution.

Side effects:

Hypotension (16% with IV), bradycardia, heart block, congestive heart failure, prolongation of the Q-T interval, arrhythmogenic effect (2-5%), with / in the introduction: asystole, cardiogenic shock, electromechanical dissociation, ventricular tachycardia.

Neurotoxic effect (20-40%, after 1 week - a few months after the initiation of therapy,remains more than a year after cancellation: signs of difficulty in walking, numbness and tingling of fingertips, uncontrolled movements, weakness in the legs), headache, dizziness, flush of blood to the face.

Photosensitivity (10%), gray-blue staining of the face, neck, hands (for treatment longer than 1 year), skin rash, hepatitis, exfoliative dermatitis, vasculitis, alopecia.

Fibrosis of the lungs or interstitial pneumonitis (10-15%, reversible after the abolition of amiodarone, treatment with glucocorticoids, in 10% of cases, the outcome is fatal).

Nausea, vomiting, deterioration of appetite, dullness of taste, pain, heaviness in epigastrium, constipation, diarrhea, flatulence, with prolonged use - toxic hepatitis (jaundice, cholestasis), liver cirrhosis.

Hyperthyroidism (2%) or hypothyroidism (10%), decreased libido, impotence; constipation, loss of appetite, bitter and metallic taste in the mouth.

Blurred vision, dryness, increased sensitivity to light, pigment deposits in the cornea (10%, reversible after cancellation).

Overdose:

Bradycardia, AV-blockade, hypotension. Treatment symptomatic.

Interaction:

Azoles, fluoroquinolones, macrolides - prolongation of the Q-T interval.

Acenocoumarol, warfarin - Increased anticoagulant effect.

Grapefruit juice, indinavir - increased plasma concentrations of amiodarone.

Diuretics - an increased risk of arrhythmias due to the risk of hypokalemia.

Other antiarrhythmics, β-adrenoblockers, BCCC, fentanyl - increased cardiodepressive action, increased probability of prolongation of the Q-T interval, arrhythmogenic action.

Inhibitors of HMG coenzyme A-reductase (statins) - the risk of myotonia, rhabdomyolysis.

Inductors and inhibitors of CYP3A4 - possible development of toxic effects.

Methotrexate is a metabolic disorder of methotrexate.

Preparations of iodine, including radioactive, is a violation of iodine uptake by the thyroid gland.

Cardiac glycosides - an increase in the plasma concentration of digoxin and, possibly, other glycosides.

Quinidine, procainamide, flecainide, phenytoin, cardiac glycosides, anticoagulants (coumarin derivatives), theophylline - increased plasma concentrations, increased action and / or toxicity when used simultaneously with amiodarone.

Cyclosporine - increased plasma concentrations of cyclosporine.

Special instructions:

Monitoring of ALT, AST, APF; auscultation, chest x-ray (before the start of therapy,3 and 6 months after it), ECG, amiodarone level in plasma, FVD, thyroid function, bronchoscopy (with the development of toxic phenomena from the lungs); examination of the ophthalmologist.

Antiarrhythmic remedy III class, a structural analogue of thyroid hormones; part of antiarrhythmic and side effects is due to binding to their intracellular receptors. Highly lipophilic.

With bradycardia, the elongation of the action potential causes pirouette tachycardia. In people with atrial fibrillation, pirouette tachycardia can occur with a decrease in heart rate after restoring the rhythm.

Elimination is slow, skipping 1-2 doses usually does not lead to arrhythmia.

Amiodarone reduces overall mortality by 10%, the risk of sudden cardiac death by 19%, and overall cardiac mortality in patients at high risk of fatal outcome (after myocardial infarction with severe ventricular rhythm disturbances, with heart failure).

Prophylactic use of amiodarone (400 mg / day for 28 days, 800 mg / day for 14 days, maintaining a dose up to 6 months) in patients with acute myocardial infarction reduces the risk of death by 13% by reducing the risk of sudden arrhythmic death by 29 %.Does not affect nonarrhythmic mortality.

Amiodarone is more effective than sotalol and propafenone, prevents recurrence of atrial fibrillation with prolonged therapy (16 months)

The probability of side effects with low doses of amiodarone (up to 400 mg / day) compared with placebo (odds ratio, OR): thyroid pathology - 4,2; neurological - 2.0; cutaneous - 2,5; from the side of the eyes - 3,4; bradycardia - 2.2; from the side of the lungs - 2.0. There is no difference from placebo in the frequency of hepatotoxic and gastrointestinal side effects.

Amiodarone (duration of therapy up to 12 months) is more effective than flecainide and quinidine, preserves the sinus rhythm in patients with atrial fibrillation.

Reduces the frequency of atrial fibrillation, ventricular tachyarrhythmias and stroke, and also shortens the period of hospitalization in people who underwent cardiac surgery.

Previous therapy with amiodarone increases the risk of respiratory failure in the early postoperative period after heart surgery. Do not use amiodarone with ventricular arrhythmias, until the need for surgical intervention is determined

Instructions

Amiodarone (Amiodaronum)