Vero-Amiodarone - instructions for use, dose, side effects, contraindications

Amiodarone refers to III (class of inhibitors of repolarization) and has a unique mechanism of antiarrhythmic action, in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (blockade of sodium channels), class IV antiarrhythmics (calcium channel blockade) and β- blocking action.

In addition to antiarrhythmic action amiodarone has antianginal, coronary dilatory, α- and β-adrenoblocking effects.

The mechanism of antiarrhythmic action:

- an increase in the duration of the third phase of the action potential of cardiomyocytes, mainly due to the blocking of the ion current in the potassium channels (the effect of the class III antiarrhythmic agent in the Williams classification);

- a decrease in the automatism of the sinus node, leading to a decrease in heart rate;

- non-competitive blockade of α- and β-adrenergic receptors;

- slowing of sinoatrial, atrial and atrioventricular conduction (more pronounced with tachycardia) in the absence of changes in intraventricular conduction;

- an increase in the refractory period and a decrease in the excitability of the myocardium of the atria and ventricles, as well as an increase in the refractory period of the atrioventricular node;

- Deceleration and prolongation of the refractory period in additional beams of the atrioventricular conduction.

Other effects of amiodarone:

- reduction of oxygen consumption by myocardium due to a moderate decrease in total peripheral resistance and heart rate, as well as a decrease in myocardial contractility due to β-adrenoblocking action;

- increase in coronary blood flow due to direct effect on the smooth muscles of the coronary arteries;

- maintenance of cardiac output, despite a slight decrease in myocardial contractility, due to a decrease in overall peripheral vascular resistance and pressure in the aorta;

- influence on the exchange of thyroid hormones: inhibition of the transformation of thyroxine (T4) into triiodothyronine (T3) (blockade of thyroxine-5-deiodinase) and blocking the seizure of these hormones by cardiomyocytes and hepatocytes,leading to a weakening of the stimulating effect of thyroid hormones on the myocardium;

- restoration of cardiac activity in cardiac arrest caused by ventricular fibrillation resistant to cardioversion.

Pharmacokinetics:

With intravenous administration of amiodarone, its activity reaches a maximum after 15 minutes and disappears approximately 4 hours after administration. After intravenous (iv) administration, the concentration of amiodarone in the blood plasma decreases rapidly due to the entry of amiodarone into the tissue. In the absence of repeated injections amiodarone gradually output. With the resumption of its administration or when the drug is administered orally amiodarone accumulates in the tissues. It has a large volume of distribution and can accumulate in almost all tissues, especially in adipose tissue and in addition to it in the liver, lungs, spleen and cornea. Penetrates through the blood-brain barrier and the placenta, is secreted with breast milk. The connection with plasma proteins is 95% (62% with albumin, 33.5% with β-lipoproteins).

Metabolised in the liver. The main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the basic compound. Amiodarone is an inhibitor of cytochrome P450 isoenzymes: CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP3A7.

It is mainly excreted through the intestine. Removal of amiodarone is very slow. Amiodarone and its metabolites are determined in blood plasma for 9 months after discontinuation of treatment. Amiodarone and its metabolites are not dialyzed.

Indications:

Cessation of paroxysmal tachycardia:

relief of paroxysmal tachycardia;
suppression of attacks of supraventricular paroxysmal tachycardia with a high frequency of contractions of the ventricles (especially against the background of Wolff-Parkinson White syndrome).

Cupping of paroxysmal and resistant tahisistolicheskoy form of atrial fibrillation (atrial fibrillation) and atrial flutter.

Cardioreanimation in case of cardiac arrest caused by ventricular fibrillation resistant to cardioversion.

Contraindications:

- Hypersensitivity to amiodarone, iodine or excipients of the drug;

- syndrome of weakness of the sinus node (SSSU) (sinus bradycardia, sinoatrial blockade) in the absence of an artificial pacemaker (pacemaker) (danger of "stopping" the sinus node);

- atrioventricular block II-III degree (in the absence of a permanent pacemaker);

- violation of intraventricular conduction (two- and three-beam blockades) in the absence of a permanent artificial pacemaker (pacemaker). With such conduction disorders, the use of amiodarone intravenously is possible only in specialized departments under the guise of a temporary pacemaker (pacemaker);

- simultaneous use with drugs that can lengthen the interval QT and cause the development of paroxysmal tachycardia, including polymorphic ventricular tachycardia such as "pirouette" (see "Interaction with other drugs");

- antiarrhythmics: IA class (quinidine, hydroquinidine, disopyramide, procainamide); antiarrhythmic drugs of the III class (dofetilide, ibutilid, brethil tosylate); sotalol;

- other (non-antiarrhythmic) drugs, such as beprideal; wincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine; astemizole, terfenadine; fluoroquinolones.

- congenital or acquired lengthening interval QT;

- severe arterial hypotension, collapse, cardiogenic shock;

- hypokalemia, hypomagnesemia;

- dysfunction of the thyroid gland (hypothyroidism, hyperthyroidism);

- pregnancy and the period of breastfeeding (see "Application during pregnancy and during breastfeeding");

- age to 18 years (efficacy and safety not established).

All of the above contraindications do not apply to the use of the drug Vero-amiodarone for cardiac recovery in case of cardiac arrest caused by ventricular fibrillation resistant to cardioversion.

Carefully:

Arterial hypotension, decompensated or severe chronic heart failure (CHF) (III and IV functional class by classification NYHA), severe respiratory failure, bronchial asthma, hepatic insufficiency, elderly age (high risk of severe bradycardia), atrioventricular blockade of the 1st degree.

Pregnancy and lactation:

Currently available clinical information is not sufficient to determine whether embryos can develop or develop in the first trimester of pregnancy. Since the fetal thyroid begins to bind iodine from the 14th week of pregnancy, then it is not expected that amiodarone will affect it if it is used earlier. Excess iodine in the use of amiodarone after the 14th week of pregnancy can lead to the appearance of laboratory symptoms of hypothyroidism in a newborn or even to the formation of a clinically significant goiter in it. Due to the effect of the drug on the thyroid gland of the fetus, amiodarone contraindicated during pregnancy, except in special cases when the expected benefit exceeds the possible risk (with life-threatening ventricular arrhythmias).

Amiodarone is excreted in breast milk in significant amounts, so it is contraindicated in the period of breastfeeding.If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Intravenously.

Injectable form of the drug Vero-amiodarone is intended for use in those cases when rapid achievement of antiarrhythmic effect is required, or if it is impossible to administer the drug inside.

Except for urgent clinical situations, the drug should be used only in the hospital, in the intensive care unit under the constant monitoring of the ECG and blood pressure!

With IV administration, the drug Vero-amiodarone should not be mixed with other drugs or simultaneously administered other drugs through the same venous access. Apply only in diluted form. To dilute the drug Vero-amiodarone, only 5% dextrose (glucose) solution should be used. Due to the peculiarities of the dosage form of the drug, it is not recommended to use the concentration of the infusion solution less than 2 ml in 500 ml of 5% dextrose (glucose) obtained by dilution.

To avoid reactions at the site of administration amiodarone should be administered through a central venous catheter,with the exception of cases of cardioversion in ventricular fibrillation resistant to cardioversion, when peripheral veins (the largest peripheral vein with maximum blood flow) can be used to administer the drug (see "Special instructions").

Severe disturbances of the heart rhythm, in cases when it is impossible to take the medication internally (with the exception of cases of cardiac recovery in case of cardiac arrest caused by ventricular fibrillation resistant to cardioversion)

Intravenous drip introduction through the central venous catheter

Usually, the loading dose is 5 mg / kg body weight in 250 ml of a 5% dextrose (glucose) solution and administered whenever possible using an electronic pump for 20-120 minutes. It can be re-injected 2-3 times within 24 hours. The rate of administration of the drug is adjusted depending on the clinical effect. The therapeutic effect appears during the first minutes of administration and gradually decreases after discontinuation of infusion, therefore, if it is necessary to continue treatment with the injection form of amiodarone, it is recommended to switch to a permanent intravenous drip introduction of the drug.

Maintenance dose: 10-20 mg / kg / 24 hours (usually 600-800 mg, but can be increased to 1200 mg for 24 hours) in 250 ml of 5% dextrose (glucose) solution for several days. From the first day of infusion, a gradual transition to amiodarone intake should begin (3 tablets of 200 mg per day). The dose can be increased to 4 or even 5 tablets of 200 mg per day.

Cardioreanimation in cardiac arrest caused by ventricular fibrillation resistant to cardioversion

Intravenous jet injection (see "Special instructions")

The first dose is 300 mg (or 5 mg / kg) of the drug Vero-amiodarone, after dilution in 20 ml of a 5% solution of dextrose (glucose) and injected intravenously.

If fibrillation does not stop, then an additional intravenous jet of the drug at a dose of 150 mg (or 2.5 mg / kg) is possible.

Side effects:

The frequency of side effects was determined as follows: very often (≥ 10%), often (≥ 1%, <10%); infrequently (≥ 0.1%, <1%); rarely (≥ 0.01%, <0.1%) and very rarely, including individual messages (<0.01%), the frequency is unknown (according to the available data, the frequency can not be determined).

From the side of the cardiovascular system:

Often

- Bradycardia (usually a moderate decrease in heart rate).

- Reduced blood pressure, usually mild and transient. Cases of severe arterial hypotension or collapse were observed in overdose or too rapid administration of the drug.

Rarely

- Proaritmogenic effect (there are reports of the occurrence of new arrhythmias including polymorphic ventricular tachycardia such as pirouettes, or exacerbation of existing, in some cases - followed by cardiac arrest), but in amiodarone it is less expressed than most antiarrhythmic agents. These effects are observed mainly in cases of amiodarone in combination with drugs that prolong the period of repolarization of the ventricles of the heart (interval QT) or in cases of electrolyte balance disturbances (see "Interaction with Other Drugs"). In the light of the available data, it is impossible to determine whether the occurrence of these rhythm disturbances is caused by amiodarone, or is associated with the severity of the cardiovascular pathology, or is a consequence of ineffective treatment.

- Pronounced bradycardia or, in exceptional cases, stopping the sinus node (in patients with sinus node dysfunction and elderly patients).

- "Tides" of blood to the skin of the face.

- Progression of heart failure (possible with intravenous jet injection).

From the endocrine system:

Rarely

- Syndrome of inadequate secretion of antidiuretic hormone (SNSAG).

Frequency unknown

- Hyperthyroidism.

From the respiratory system:

Rarely

- Cough, shortness of breath, interstitial pneumonitis.

- Bronchospasm and / or apnea in patients with severe respiratory failure, especially in patients with bronchial asthma.

- Acute respiratory distress syndrome, sometimes with a fatal outcome and immediately after surgery (the possibility of interaction with high doses of oxygen is assumed) (see "Special instructions").

From the musculoskeletal and connective tissue:

Frequency unknown

- Pain in the lumbar and lumbosacral spine.

From the digestive system:

Often

- Nausea.

Rarely

- Isolated increase in the activity of "hepatic" transaminases in the serum, usually moderate (1.5-3 times the normal values) and decreasing with decreasing dose or even spontaneously.

- Acute liver damage (within 24 hours after amiodarone administration) withincreased transaminase activity and / or jaundice, including the development of hepatic insufficiency, sometimes fatal (see "Special instructions").

Frequency unknown

- Decreased appetite.

- Pancreatitis / acute pancreatitis.

- Dryness of the oral mucosa.

- Constipation.

From the skin:

Rarely

- Feeling of heat, increased sweating.

Frequency unknown

- Eczema, hives, severe skin reactions, sometimes fatal, including toxic epidermal necrolysis / Stevens-Jones syndrome, bullous dermatitis.

From the central nervous system:

Rarely

- Benign intracranial hypertension (pseudotumor of the brain), headache.

Frequency unknown

- Parkinsonism.

- Parosmia.

- Confusion / delirium.

- Hallucinations.

From the immune system:

Frequency unknown

- Angioedema (edema of Quincke).

- Anaphylactic and anaphylactoid reactions, including anaphylactic shock.

- Drug reaction with eosinophilia and systemic symptoms.

Reactions at the site of administration:

Often

- Reactions at the site of administration, such as pain, erythema, edema, necrosis, transudation, infiltration, inflammation, compaction, thrombophlebitis, phlebitis, cellulitis, infection, pigmentation.

On the part of the blood and lymphatic system:

Frequency unknown

- Neutropenia, agranulocytosis.

Other:

Frequency unknown

- Decreased libido.

Overdose:

Symptoms: Information on the overdose of the injection form of amiodarone is absent. There is information regarding the acute overdose of amiodarone taken internally in tablets. Several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal tachycardia such as pirouette, circulatory disorders and liver function, marked decrease in blood pressure are described.

Treatment: symptomatic (with bradycardia - appointment β-adrenostimulyatorov or installation of a pacemaker, with tachycardia such as "pirouette" - iv injection of magnesium salts, pacing pacemaking).

Neither amiodarone, nor its metabolites are removed during hemodialysis. There is no specific antidote.

Interaction:

Severe arrhythmia, such as polymorphic ventricular tachycardia of the pirouette type, can be caused by a number of drugs, especially antiarrhythmics IA and class III and some neuroleptics (see below). Predisposing factors for its development may be hypokalemia, bradycardia, congenital or acquired lengthening of the interval QT.

Contraindicated combinations (see "Contraindications"):

- With drugs that can cause a polymorphic ventricular tachycardia such as "pirouette" (when combined with amiodarone, the risk of potentially lethal ventricular pirouette tachycardia increases):

antiarrhythmics: IA class (quinidine, hydroquinidine, disopyramide, procainamide), Class III (dofetilide, ibutilide, brethil tosylate), sotalol;
other (non-antiarrhythmic) drugs, such as beprideal; wincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine; astemizole, terfenadine; fluoroquinolones (in particular moxifloxacin).

Uncommon combinations:

- FROM βadrenoblockers, blockers of "slow" calcium channels, slowing heart rate (verapamil, diltiazem), t. there is a risk of developing violations of automatism (pronounced bradycardia) and conduction.

- With laxatives, stimulating peristalsis of the intestine, since can cause hypokalemia, which increases the risk of developing ventricular tachycardia such as "pirouette."

Combinations requiring caution when used:

- With drugs that can cause hypokalemia:

diuretics that cause hypokalemia (in monotherapy or combination);
amphotericin B (IV);
systemic glucocorticosteroids;
tetracosactide.

An increased risk of developing ventricular arrhythmias, especially ventricular pirouette tachycardia (hypokalemia is a predisposing factor). It is necessary to monitor the concentration of electrolytes in the blood, if necessary, correction of hypokalemia and constant clinical and electrocardiographic monitoring of the patient. In the case of development of ventricular tachycardia of the "pirouette" type, antiarrhythmics should not be used (ventricular pacing should be started,possibly intravenous administration of magnesium salts).

- With procainamide (see "Interaction with other medicines: contraindicated combinations")

Amiodarone can increase the plasma concentration of procainamide and its metabolite N-acetylprocainamide, which may increase the risk of side effects of procainamide.

- With anticoagulants of indirect action

Amiodarone increases the concentration of warfarin by inhibiting the isoenzyme CYP2C9. With the combination of warfarin with amiodarone, the effects of an indirect anticoagulant may increase, which increases the risk of bleeding. It should be more often monitored prothrombin time (calculation of the international normalized ratio (INR)) and to correct the doses of anticoagulant both during treatment with amiodarone and after its withdrawal.

- With dabigatran

Caution should be exercised when using amiodarone with dabigatran at the same time because of the risk of bleeding. Dabigatran dose may need to be adjusted in accordance with the instructions in its instructions for use.

- FROM cardiac glycosides (digitalis preparations)

The possibility of violations of automatism (pronounced bradycardia) and atrial-ventricular conduction. In addition, with the combination of digoxin with amiodarone, an increase in the concentration of digoxin in the blood plasma is possible (due to a decrease in its clearance). Therefore, when digoxin is combined with amiodarone, it is necessary to determine the concentration of digoxin in the blood and to monitor possible clinical and electrocardiographic manifestations of glycoside intoxication. You may need to reduce the dosage of digoxin.

- FROM esmolol

Violations of contractility, automatism and conduction (suppression of compensatory reactions of the sympathetic nervous system). Clinical and ECG monitoring is required.

- With phenytoin (and, by extrapolation, with fosphenytoin)

Amiodarone can increase plasma concentrations of phenytoin by inhibiting the isoenzyme CYP2C9, therefore, when phenytoin is combined with amiodarone, an overdose of phenytoin may develop, which can lead to the appearance of neurologic symptoms; requires clinical monitoring and, at the first signs of an overdose, a decrease in the dose of phenytoin, it is desirable to determine the concentration of phenytoin in the blood plasma.

- With flecainide

Amiodarone increases the plasma concentration of flecainide by inhibiting the isoenzyme CYP2D6, in connection with which correction of doses of flecainide is required.

- With drugs metabolized by isoenzyme CYP3A4

When combined amiodarone, inhibitor of isoenzyme CYP3A4, these preparations can increase their plasma concentrations, which can lead to an increase in their toxicity and / or increased pharmacodynamic effects and may require a reduction in their doses. Below are listed such preparations:

- Cyclosporin

It is possible to increase the concentration of cyclosporine in the blood plasma, associated with a decrease in the metabolism of the drug in the liver, which may increase the nephrotoxic effect of cyclosporine. It is necessary to determine the concentration of cyclosporin in the blood, monitor kidney function and correct the dosage regimen of cyclosporine during the treatment with amiodarone and after drug withdrawal.

- Fentanyl

The combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects.

- Other drugs metabolized by isoenzyme CYP3A4: lidocaine (risk of developing sinus bradycardia and neurologic symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (the risk of increasing its side effects), midazolam (risk of development of psychomotor effects), triazolam, dihydroergotamine, ergotamine, simvastatin and other statins metabolized by isoenzyme CYP3A4 (increased risk of muscle toxicity, rhabdomyolysis, so the dose of simvastatin should not exceed 20 mg per day, if it is ineffective, you should switch to another statin that is not metabolized by the CYP3A4 isoenzyme).

- With orlistat

The risk of reducing the concentration of amiodarone and its active metabolite in the blood plasma. Clinical and, if necessary, ECG monitoring is required.

- With clonidine, guanfacin, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine methylsulfate), pilocarpine

The risk of developing excessive bradycardia (cumulative effect).

- With cimetidine, grapefruit juice

Slowing down the metabolism of amiodarone and increasing its plasma concentrations, it is possible to increase the pharmacodynamic and side effects of amiodarone.

- With preparations for inhalation anesthesia

The possibility of developing the following severe complications in patients receiving amiodarone, when they receive anesthesia: bradycardia (resistant to atropine), arterial hypotension, conduction disorders, reduction of cardiac output.

There were very rare cases of severe complications from the respiratory system (acute respiratory distress syndrome of adults), sometimes fatal, which developed immediately after surgery, the occurrence of which is associated with high concentrations of oxygen.

- With radioactive iodine

Amiodarone contains in its composition iodine and therefore can disrupt the uptake of radioactive iodine, which can distort the results of a radioisotope study of the thyroid gland.

- With rifampicin

Rifampicin is a potent inducer of isoenzyme CYP3A4, when combined with amiodarone, it can reduce the plasma concentrations of amiodarone and desethylamiodarone.

- With preparations of St. John's wort perfumed

St. John's wort is a potent inducer of isoenzyme CYP3A4. In connection with this, it is theoretically possible to reduce the plasma concentration of amiodarone and reduce its effect (no clinical data are available).

- With HIV protease inhibitors (incl. indinavir)

HIV protease inhibitors are inhibitors of the isoenzyme CYP3A4. With simultaneous use with amiodarone may increase the concentration of amiodarone in the blood.

- With clopidogrel

Clopidogrel, which is an inactive thienopyridine drug, is metabolized in the liver with the formation of active metabolites. Possible interaction between clopidogrel and amiodarone, which can lead to a decrease in the effectiveness of clopidogrel.

- With dextromethorphan

Dextromethorphan is a substrate of isoenzymes CYP2D6 and CYP3A4. Amiodarone inhibits these cytochrome P450 isoenzymes and can theoretically increase the plasma concentration of dextromethorphan.

Special instructions:

Except for urgent cases, intravenous amiodarone should be administered only in the intensive care unit with constant monitoring of the ECG (due to the possibility of developing bradycardia and pro-arrhythmogenic action) and lowering blood pressure.

The injection form of amiodarone should be administered only as an infusion (with the exception of cases of cardiac recovery in case of cardiac arrest caused by ventricular fibrillation resistant to cardioversion (see Fig."Method of administration and dose"), t. even a very slow intravenous fluid injection can cause an excessive decrease in blood pressure, heart failure, or severe respiratory failure.

In order to avoid the occurrence of reactions at the site of injection (see "Side effect"), the injection form of amiodarone is recommended to be administered through a central venous catheter. Only in the case of cardiac recovery in case of cardiac arrest caused by ventricular fibrillation resistant to cardioversion, in the absence of central venous access (no established central venous catheter), the injection form of amiodarone can be injected into a large peripheral vein with maximum blood flow.

If, after cardiac recovery, amiodarone treatment should continue, the drug should be injected intravenously via a central venous catheter under a constant control of blood pressure and ECG.

Amiodarone should not be mixed in one syringe or dropper with other medications.

In connection with the possibility of the development of interstitial pneumonitis after the appearance of pronounced dyspnea after the administration of amiodarone ordry cough, both accompanied and not accompanied by a deterioration in the general condition (increased fatigue, fever) requires chest radiography and, if necessary, cancel the drug, since interstitial pneumonitis can lead to the development of pulmonary fibrosis. However, these phenomena are mainly reversible in the early cancellation of amiodarone with the appointment of glucocorticosteroids or without their appointment. Clinical manifestations usually disappear within 3-4 weeks. Restoration of the radiographic picture and function of the lungs takes place more slowly (several months).

After mechanical ventilation of the lungs (for example, when surgical interventions are administered) in patients who have been injected amiodarone, there were rare cases of development of acute respiratory distress syndrome, sometimes with a lethal outcome (it is assumed that it is possible to interact with high doses of oxygen). Therefore, it is recommended to exercise strict control over the condition of such patients.

In patients who receive long-term treatment with amiodarone for heart rhythm disturbances,reported increased frequency of ventricular fibrillation and / or an increase in the sensitivity threshold of a pacemaker or an implanted artificial pacemaker, which may reduce their effectiveness. Therefore, before and during treatment with amiodarone, the correctness of their functioning should be regularly monitored.

Due to the prolongation of the repose period of the ventricles of the heart, the pharmacological action of amiodarone causes certain changes in the ECG: lengthening of the interval QT, QTc (corrected), possibly the appearance U waves. Allowable elongation QT - no more than 450 ms or no more than 25 % of the initial value. These changes are not a manifestation of the toxic effect of the drug, but require monitoring for correcting the dose and evaluating the possible proarhythmogenic effect. When developing AV blockades II-III degree, sinoatrial blockade or a two-beam intraventricular blockade, treatment with amodarone should be discontinued. When AV blockade of the I degree, it is necessary to strengthen patient monitoring.

In the event of visual impairment (blurred vision, reduced visual acuity), a complete ophthalmological examination, including examination of the fundus, is necessary.With the development of optic neuropathy or optic neuritis, amiodarone treatment is discontinued because of the risk of developing blindness.

During the first 24 hours after the injection of the amiodarone injection form, severe acute liver damage can develop with the development of hepatic insufficiency, sometimes with a fatal outcome. It is recommended that liver function be checked regularly before starting amiodarone and regularly during amiodarone treatment. When the activity of "hepatic" transaminases increases, which is 3 times higher than the upper limit of the norm, the dose of amiodarone should be reduced or stopped.

General anesthesia. Before surgery, an anesthesiologist should be informed that the patient is receiving amiodarone. Treatment with amiodarone may increase the hemodynamic risk inherent in local or general anesthesia. In particular, this refers to its bradycardic and hypotensive effects, reduction in cardiac output and conduction disorders.

Combinations with β-adrenoblockers, in addition to sotalol (a contraindicated combination) and esmolol (a combination that requires extreme caution when used),verapamil and diltiazem can be considered only in the context of prophylaxis of life-threatening ventricular arrhythmias and in the case of restoration of cardiac activity in cardiac arrest caused by ventricular fibrillation resistant to cardioversion.

Disorders of electrolyte balance, especially hypokalemia: it is important to take into account situations that may be accompanied by hypokalemia, as predisposing to pro-arrhythmic effects. Hypokalemia should be corrected before starting amiodarone.

Side effects of the drug (see "Side effect") usually depend on the dose; therefore, care should be taken when determining the minimum effective maintenance dose to avoid or minimize the occurrence of unwanted effects.

Amiodarone can cause thyroid dysfunction, especially in patients with thyroid dysfunction in their own or family history. Therefore, in case of switching to amiodarone intake during treatment and several months after the end of treatment, a thorough clinical and laboratory monitoring should be carried out.If there is a suspicion of thyroid dysfunction, the concentration of T3, T4 and TSH in serum should be determined.

Clinical manifestations are usually mild, so symptoms such as weight loss, the occurrence of rhythm disorders, angina attacks, the development of CHF, should alert the doctor. The diagnosis is confirmed by the detection of a decrease in the concentration of thyroid-stimulating hormone (TSH) in the serum, determined with the help of ultrasensitive TSH analysis. In this case, the reception of amiodarone should be stopped. Recovery usually occurs within a few months after the withdrawal of treatment. First, there is a disappearance of clinical manifestations, then normalization of indicators of thyroid function evaluation occurs. Severe cases of thyrotoxicosis, which can sometimes lead to death (both due to thyrotoxicosis itself and due to a dangerous imbalance between myocardial oxygen demand and delivery) require urgent therapy. Treatment should be selected in each case individually: antithyroid drugs (which may not always be effective), glucocorticosteroids, β-adrenoblockers.

Perhaps the inhibition of bone marrow function, manifested by the development of normocyte normochromic anemia, thrombocytopenia or neutropenia, granuloma formation is possible, in addition post-development studies or observations revealed cases of agranulocytosis, hemolytic anemia, pancytopenia. Symptoms may regress after withdrawal of the drug and the appointment of glucocorticosteroids, with the repeated administration of the drug may be their recurrence.

Against the background of taking amiodarone, it is possible to develop unwanted phenomena from the psyche, including a change in consciousness, hallucinations and delirium. Possible resistance of the developed state to the use of benzodiazepine drugs, it is necessary to cancel amiodarone.

The use of amiodarone can cause the development of unpleasant phenomena on the skin side, the most frequently reported development of increased photosensitivity and skin tone change (more often in patients younger than 60 years), less often - reversible alopecia.

Possible development of severe adverse events, including toxic epidermal necrolysis, exfoliative dermatitis, bullous dermatosis, cutaneous vasculitis, linear IgA-dependent dermatosis, psoriasis, skin cancer, skin itch.

Patients should be instructed about the possibility of developing photosensitization reactions, the need to avoid exposure to sunlight and the use of sunscreen if necessary. Increased sensitivity to sunlight can persist for several months after the abolition of amiodarone. In most cases, the manifestations are limited to sensations of redness, burning or "twitching" of the skin exposed to intense sunlight, but it is possible to develop severe phototoxic reactions. Hypersensitivity reactions against the background of the use of the drug include the above cutaneous, as well as anaphylactic and anaphylactoid reactions, including shock, angioneurotic edema, lupus erythematosus, drug reaction with eosinophilia and systemic symptoms. It is possible to develop cross-allergic reactions to amiodarone in patients with hypersensitivity to iodine-containing contrast agents.

In children, the safety and efficacy of amiodarone has not been studied. The injectable form of Vero-amiodarone contains benzyl alcohol.There have been reports of cases of development in newborns of severe asthma with a fatal outcome after intravenous administration of solutions containing benzyl alcohol.

Form release / dosage:

Solution for intravenous administration, 50 mg / ml.

Packaging:

To 3 ml in neutral glass ampoules with a capacity of 5 ml.

By 5 or 10 ampoules in a box of cardboard or a pack of cardboard with partitions or a liner of paper.

5 ampoules in a contour cell box made of a polyvinylchloride film and aluminum foil printed lacquered or foil-free.

1 Contour mesh packaging in a pack of cardboard.

In each box or bundle, the instruction manual and the opener for opening ampoules or the scarifier are ampoule.

When using ampoules with a notch or rupture ring, the ampoule scaler or knife for opening ampoules is not inserted.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N002637 / 01

Date of registration:26.05.2008 / 16.09.2015

Expiration Date:Unlimited

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Representation: & nbspVEROPHARM, AO VEROPHARM, AO Russia

Information update date: & nbsp02.02.2017

Illustrated instructions

Instructions

Vero-Amiodarone (Vero-Amiodarone)