Vero-amiodarone 50mg/ml 3 ml, 5 pcs.

The antiarrhythmic drug of class III, has antianginal action.

The antiarrhythmic effect is associated with the ability to increase the duration of action potential of cardiomyocytes and effective refractory period of atria, ventricles, AV node, Gis bundle, Purkinje fibers. This is accompanied by decreased automatism of sinus node, deceleration of AV conduction, reduced excitability of cardiomyocytes.

It is believed that the mechanism of increase of action potential duration is connected with potassium channel blockade (potassium ions excretion from cardiomyocytes decreases). By blocking inactivated “fast” sodium channels, it has effects typical for class I antiarrhythmic agents. Inhibits slow (diastolic) depolarization of sinus node cell membrane, causing bradycardia, inhibits AV conduction (effect of class IV antiarrhythmics).

The antianginal effect is due to coronary dilator and antiadrenergic effect, reduction of myocardial oxygen demand. It has an inhibitory effect on the α- and β-adrenoreceptors of the cardiovascular system (without complete blockade). Reduces sensitivity to sympathetic nervous system hyperstimulation and coronary vascular tone; increases coronary blood flow; decreases HR; increases myocardial energy reserves (by increasing creatine sulfate, adenosine and glycogen). Reduces RPS and systemic BP (when administered intravenously).

It is believed that amiodarone may increase phospholipid levels in tissues.

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 weakening the stimulating effect of thyroid hormones on the myocardium (T3 deficiency can lead to its hyperproduction and thyrotoxicosis).

When taken orally, the onset of action is from 2-3 days to 2-3 months, and 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%. Cmax in blood plasma is reached after 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 Vd and is characterized by slow achievement of equilibrium and therapeutic plasma concentrations and to prolonged excretion. Amiodarone is determined in plasma up to 9 months after discontinuation of its use. Protein binding is high – 96% (62% with albumin, 33.5% with β-lipoproteins).

It penetrates through HEB and placental barrier (10-50%), is excreted with breast milk (25% of dose received by mother).

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

The excretion is biphasic. After oral administration, the T1/2 is 4-21 days in the initial phase and 25-110 days in the terminal phase; desethylamiodarone averages 61 days. Generally, the T1/2 of oral administration of amiodarone is 14-59 days. After IV administration of amiodarone, the T1/2 in the terminal phase is 4-10 days. It is excreted mainly with bile through the intestine, a small enterohepatic recirculation may be observed. Very small amounts of amiodarone and desethylamiodarone are excreted in the urine.

Amiodarone and its metabolites are not excreted by dialysis.

Indications

Treatment and prevention of paroxysmal rhythm disturbances: 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 associated with WPW syndrome), including atrial fibrillation and atrial flutter.

Atrial and ventricular extrasystoles; arrhythmias associated with coronary artery disease or chronic heart failure, parasystoles, ventricular arrhythmias in patients with Chagas’ myocarditis; angina pectoris.

Active ingredient

Composition

Intravenous solution 5% 1 amp 1 ml

Amiodarone hydrochloride 150 mg 50 mg

How to take, the dosage

In adults, the initial single dose is 200 mg when taken orally. For children the dose is 2.5-10 mg/day. The regimen and duration of treatment are determined individually.

For intravenous administration (by stream or drop), the single dose is 5 mg/kg; the daily dose is up to 1.2 g (15 mg/kg).

Interaction

Drug interaction of amiodarone with other drugs is possible even several months after the end of its use due to the long T1/2.

The concomitant use of amiodarone and class I A antiarrhythmic drugs (including disopyramide) increases QT interval due to the additive effect on its value and increases the risk of ventricular pirouette tachycardia.

The concomitant use of amiodarone with laxatives, which may cause hypokalemia, increases the risk of ventricular arrhythmias.

Medications that cause hypokalemia, including diuretics, corticosteroids, amphotericin B (IV), tetracosactide, when used concomitantly with amiodarone increase QT interval and increase risk of ventricular arrhythmias (including pirouette type).

The concomitant use of agents for general anesthesia and oxygen therapy causes risk of bradycardia, arterial hypotension, conduction disturbances, decreased cardiac stroke volume, which seems to be caused by additive cardiodepressive and vasodilatory effects.

Tracyclic antidepressants, phenothiazines, astemizole, terfenadine when used concomitantly may increase QT interval and risk of ventricular arrhythmias, particularly pirouette type.

Concomitant use of warfarin, phenprocoumon, acenocoumarol increases the anticoagulant effect and increases the risk of bleeding.

Concomitant use of vincamine, sultopride, erythromycin (IV), pentamidine (IV, IV/m) increases the risk of pirouette-type ventricular arrhythmias.

Concomitant use may increase plasma dextromethorphan concentration due to decreased rate of its metabolism in the liver, which is caused by inhibition of CYP2D6 isoenzyme activity of cytochrome P450 system under the influence of amiodarone and delayed excretion of dextromethorphan from the body.

Concomitant use of digoxin significantly increases plasma concentrations of digoxin due to decreased clearance and thereby increases the risk of digitalis intoxication.

Concomitant use of diltiazem, verapamil increases negative inotropic effects, bradycardia, conduction disorders, AV-blockade.

A case of increased plasma concentrations of amiodarone when used concomitantly with indinavir has been described. Ritonavir, nelfinavir, and saquinavir are thought to have similar effects.

The concomitant use of colestyramine decreases plasma concentrations of amiodarone due to its binding to colestyramine and reduced absorption from the gastrointestinal tract.

There have been reports of increased plasma concentrations of lidocaine when used concomitantly with amiodarone and development of seizures, apparently due to inhibition of lidocaine metabolism by amiodarone.

Possible synergism is thought to be possible with respect to sinus node depressant effects.

The simultaneous use of lithium carbonate may cause hypothyroidism.

Concomitant use of procainamide increases QT interval due to its additive effect on its magnitude and the risk of developing pirouette-type ventricular tachycardia. Increased plasma concentrations of procainamide and its metabolite N-acetylprocainamide and increased side effects.

Concomitant use of propranololol, metoprolol, sotalol may cause arterial hypotension, bradycardia, ventricular fibrillation, asystole.

A case of pirouette arrhythmia has been described with concomitant use of trazodone.

Concomitant use of quinidine increases QT interval due to its additive effect on its value and the risk of pirouette-type ventricular tachycardia. Increase of plasma concentration of quinidine and increase of its side effects.

In case of concomitant use there has been described an increase in side effects of clonazepam, which appears to be due to its cumulation due to inhibition of oxidative metabolism in the liver caused by amiodarone.

Concomitant use of cisapride significantly increases QT interval due to additive action, the risk of ventricular arrhythmias (including pirouette type).

Concomitant use increases the plasma concentration of cyclosporine and the risk of nephrotoxicity.

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

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

It is believed that due to inhibition of liver enzymes involved in metabolism of phenytoin under the influence of amiodarone, concentration of phenytoin in plasma may increase and its side effects may become stronger.

Induction of microsomal liver enzymes under phenytoin influence causes increase of amiodarone metabolism rate in liver and decrease of its concentration in plasma.

Special Instructions

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

Do not use in patients with severe respiratory failure.

Before starting amiodarone, a radiological study of the lungs and thyroid function should be performed, and electrolyte abnormalities should be corrected if necessary.

In long-term treatment, regular monitoring of thyroid function, consultation with an ophthalmologist, and radiological examination of the lungs are necessary.

Parenteral use should be done only in specialized hospital departments with constant monitoring of BP, HR and ECG.

Patients receiving amiodarone should avoid direct exposure to sunlight.

When amiodarone is withdrawn, heart rhythm abnormalities may recur.

May affect the results of a test of radioactive iodine accumulation in the thyroid gland.

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

Contraindications

Hypersensitivity (including to iodine), SSRI, sinus bradycardia, SA block, AV block of II-III degree (without a pacemaker), cardiogenic shock, hypokalemia, collapse, arterial hypotension, hypothyroidism, thyrotoxicosis, interstitial lung disease, taking MAO inhibitors, pregnancy, lactation. CHF, liver failure, bronchial asthma, pregnancy, lactation, old age (high risk of severe bradycardia), age under 18 years (effectiveness and safety of use have not been established).

Side effects

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

Senses: uveitis, deposition of lipofuscin in the corneal epithelium (if the deposition is significant and fills partially the pupil – complaints of luminous spots or shadows in front of the eyes in bright light), retinal microblading.

Particularly cardiac disorders: sinus bradycardia (refractory to m-cholinoblockers), AV blockade; with prolonged use – progression of CHF, “pirouette”-type tachycardia, worsening of existing arrhythmia or its occurrence; with parenteral use – decrease of BP.

Metabolism disorders: increase of T4 level with normal or insignificantly decreased T3 level, hypothyroidism, thyrotoxicosis (the drug should be discontinued).

Respiratory system disorders: with long-term use – cough, dyspnea, interstitial pneumonia or alveolitis, pulmonary fibrosis, pleurisy; with parenteral use – bronchospasm, apnea (in patients with severe respiratory failure).

Digestive system disorders: nausea, vomiting, decreased appetite, dulling or loss of sense of taste, feeling of heaviness in epigastrium, abdominal pain, constipation, flatulence, diarrhea; rarely – increased activity of liver transaminases; with long-term use – toxic hepatitis, cholestasis, jaundice, liver cirrhosis.

Laboratory measures: with prolonged use – thrombocytopenia, hemolytic and aplastic anemia. Allergic reactions: skin rash, exfoliative dermatitis. Local reactions: with parenteral use – phlebitis.

Others: myopathy, epididymitis, decreased potency, alopecia, vasculitis, photosensitization (skin hyperemia, slight pigmentation of exposed skin areas), lead-blue or bluish skin pigmentation; when parenteral use – fever, increased sweating.

Overdose.

Symptoms: bradycardia, AV blockade, BP decrease. Treatment: gastric lavage, administration of colestyramine; in bradycardia – beta-adrenergic pacemakers or pacemaker placement; in tachycardia such as “pirouette” – IV administration of Mg2+ salts, cardiostimulation. Hemodialysis is ineffective.

Similarities