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A drug Cordaron- antiarrhythmic drug.

Pharmacological properties

Amiodarone belongs to class III antiarrhythmic drugs (class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action, since in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (sodium channel blockade), class IV antiarrhythmics (calcium channel blockade ) and non-competitive beta-adrenergic blocking action.

In addition to the antiarrhythmic effect, it has antianginal, coronary dilation, alpha and beta adrenergic blocking effects.

Antiarrhythmic properties:

– an increase in the duration of the 3rd phase of the action potential of cardiomyocytes, mainly due to blocking the ion current in potassium channels (the effect of a class III antiarrhythmic according to the Williams classification);

– a decrease in the automaticity of the sinus node, leading to a decrease in heart rate;

– non-competitive blockade of alpha and beta adrenergic receptors;

– slowing of sinoatrial, atrial and atrioventricular conduction, more pronounced with tachycardia;

– no changes in ventricular conductivity;

– an increase in refractory periods 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;

– slowing down conduction and increasing the duration of the refractory period in additional atrioventricular conduction bundles.

Other effects:

– absence of negative inotropic effect when taken orally;

– reduction of oxygen consumption by the myocardium due to a moderate decrease in peripheral resistance and heart rate;

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

– maintaining cardiac output by reducing aortic pressure and reducing peripheral resistance;

– influence on the exchange of thyroid hormones: inhibition of the conversion of T3 to T4 (blockade of thyroxine-5-deiodinase) and blocking the uptake of these hormones by cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium.

Therapeutic effects are observed, on average, a week after starting to take the drug (from several days to two weeks). After stopping its use, amiodarone is detected in the blood plasma for 9 months. The possibility of maintaining the pharmacodynamic effect of amiodarone for 10-30 days after its discontinuation should be taken into account.

Pharmacokinetics

Bioavailability after oral administration varies from 30 to 80% in different patients (average value about 50%). After a single oral dose of amiodarone, maximum plasma concentrations are reached within 3-7 hours. However, the therapeutic effect usually develops a week after starting the drug (from several days to two weeks). Amiodarone is a drug with a slow release into tissues and high affinity for them.

The connection with blood plasma proteins is 95% (62% with albumin, 33.5% with beta-lipoproteins). Amiodarone has a large volume of distribution. During the first days of treatment, the drug accumulates in almost all tissues, especially in adipose tissue and, in addition to it, in the liver, lungs, spleen and cornea.

Amiodarone is metabolized in the liver via isoenzymes CYP3A4 and CYP2C8. Its main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. Amiodarone and its active metabolite desethylamiodarone in vitro have the ability to inhibit the isoenzymes CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and desethylamiodarone have also demonstrated the ability to inhibit certain transporters, such as P-glycoprotein (P-gp) and organic cation transporter (POK2). In vivo, interactions of amiodarone with substrates of the isoenzymes CYP3A4, CYP2C9, CYP2D6 and P-gp were observed.

The elimination of amiodarone begins within a few days, and the achievement of equilibrium between the intake and elimination of the drug (achievement of an equilibrium state) occurs after one to several months, depending on the individual characteristics of the patient. The main route of elimination of amiodarone is the intestine. Amiodarone and its metabolites are not eliminated by hemodialysis. Amiodarone has a long half-life with large individual variability (therefore, when selecting a dose, for example, increasing or decreasing it, it should be remembered that at least

at least 1 month for the new plasma concentration of amiodarone to stabilize). Elimination when taken orally occurs in 2 phases: the initial half-life (first phase) is 4-21 hours, the half-life in the 2nd phase is 25-110 days. After prolonged oral administration, the average half-life is 40 days. After discontinuation of the drug, complete elimination of amiodarone from the body may continue for several months.

Each dose of amiodarone (200 mg) contains 75 mg of iodine. Part of the iodine is released from the drug and is found in the urine in the form of iodide (6 mg per 24 hours with a daily dose of amiodarone 200 mg). Most of the iodine remaining in the drug is excreted through the intestines after passing through the liver, however, with prolonged use of amiodarone, iodine concentrations in the blood can reach 60-80% of amiodarone blood concentrations.

The peculiarities of the pharmacokinetics of the drug explain the use of “loading” doses, which are aimed at the rapid accumulation of amiodarone in tissues, at which its therapeutic effect is manifested.

Pharmacokinetics in renal failure: due to the insignificant excretion of the drug by the kidneys in patients with renal failure, no dose adjustment of amiodarone is required.

Indications for use

A drug Cordaron used to prevent relapses:

Life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be started in the hospital with careful cardiac monitoring).

Supraventricular paroxysmal tachycardia: documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with organic heart disease; documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients without organic heart disease, when antiarrhythmic drugs of other classes are ineffective or there are contraindications to their use; documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome.

Atrial fibrillation (atrial fibrillation) and atrial flutter. Prevention of sudden arrhythmic death in high-risk patients

Patients after a recent myocardial infarction with more than 10 ventricular extrasystoles per hour, clinical manifestations of chronic heart failure and a reduced left ventricular ejection fraction (less than 40%).

Cordarone can be used in the treatment of arrhythmias in patients with coronary heart disease and/or left ventricular dysfunction.

Mode of application

The drug Cordarone should be taken only as prescribed by a doctor.

Cordarone tablets are taken orally before meals and washed down with plenty of water.

Loading (“saturating”) dose: various saturation schemes can be used.

In the hospital: the initial dose, divided into several doses, ranges from 600 - 800 mg (up to a maximum of 1200 mg) per day until a total dose of 10 g is reached (usually within 5-8 days).

Outpatient: the initial dose, divided into several doses, is from 600 to 800 mg per day until a total dose of 10 g is reached (usually within 10 to 14 days).

Maintenance dose: may vary in different patients from 100 to 400 mg/day.

The minimum effective dose should be used according to the individual therapeutic effect.

Since Cordarone has a very long half-life, it can be taken every other day or taken 2 days a week in between.

The average therapeutic single dose is 200 mg.

The average therapeutic daily dose is 400 mg.

The maximum single dose is 400 mg.

The maximum daily dose is 1200 mg.

Side effects

From the cardiovascular system: often - moderate bradycardia, the severity of which depends on the dose of the drug. Uncommon - conduction disorders (sinoatrial block, AV block of various degrees); arrhythmogenic effect (there are reports of the emergence of new arrhythmias or aggravation of existing ones, in some cases with subsequent cardiac arrest). In light of the available data, it is impossible to determine whether this is a consequence of the drug, or related to the severity of cardiac damage, or a consequence of treatment failure. These effects are observed mainly when Cordarone® is used in conjunction with drugs that prolong the period of repolarization of the ventricles of the heart (QTc interval) or in case of electrolyte imbalance (see “Interaction”). Very rarely - severe bradycardia or, in exceptional cases, sinus node arrest, which were observed in some patients (patients with sinus node dysfunction and elderly patients). Frequency unknown - progression of chronic heart failure (with long-term use).

From the digestive system: very often - nausea, vomiting, loss of appetite, dullness or loss of taste, feeling of heaviness in the epigastrium, especially at the beginning of treatment; passing after dose reduction; isolated increase in transaminase activity in the blood serum, usually moderate (1.5-3 times higher than normal values) and decreasing with decreasing dose or even spontaneously. Often - acute liver damage with increased transaminases and/or jaundice, including the development of liver failure, sometimes fatal (see "Special Instructions"). Very rarely - chronic liver diseases (pseudoalcoholic hepatitis, cirrhosis) are sometimes fatal. Even with a moderate increase in transaminase activity in the blood, observed after treatment lasting more than 6 months, chronic liver damage should be suspected.

From the respiratory system: often - cases of interstitial or alveolar pneumonitis and bronchiolitis obliterans with pneumonia have been reported, sometimes resulting in death. Several cases of pleurisy have been reported. These changes may lead to the development of pulmonary fibrosis, but they are largely reversible with early discontinuation of amiodarone, with or without corticosteroids. Clinical manifestations usually disappear within 3–4 weeks. Recovery of the X-ray picture and lung function occurs more slowly (several months). The appearance of severe shortness of breath or a dry cough in a patient receiving amiodarone, either accompanied or not accompanied by a deterioration in general condition (increased fatigue, loss of body weight, increased body temperature), requires a chest x-ray and, if necessary, discontinuation of the drug. Very rarely - bronchospasm in patients with severe respiratory failure, especially in patients with bronchial asthma; acute respiratory distress syndrome, sometimes fatal and sometimes immediately after surgery (possibility of interaction with high doses of oxygen is expected) (see "Special Instructions"). Frequency not known - pulmonary hemorrhage.

From the senses: very often - microdeposits in the corneal epithelium, consisting of complex lipids, including lipofuscin, they are usually limited to the pupil area and do not require cessation of treatment and disappear after discontinuation of the drug. Sometimes they can cause visual disturbances in the form of a colored halo or blurred contours in bright light. Very rare - a few cases of optic neuritis/optic neuropathy have been described. Their connection with amiodarone has not yet been established. However, since optic neuritis can lead to blindness, if blurred vision or decreased visual acuity occurs while taking Cordarone®, it is recommended to perform a full ophthalmological examination, including fundoscopy, and if optic neuritis is detected, discontinue amiodarone.

Endocrine disorders: often - hypothyroidism with its classic manifestations: weight gain, chilliness, apathy, decreased activity, drowsiness, bradycardia that is excessive compared to the expected effect of amiodarone. The diagnosis is confirmed by the detection of elevated serum TSH levels. Normalization of thyroid function is usually observed within 1–3 months after cessation of treatment. In life-threatening situations, treatment with amiodarone can be continued, with simultaneous additional administration of L-thyroxine under monitoring of serum TSH levels. Hyperthyroidism, the appearance of which is possible during and after treatment (cases of hyperthyroidism that developed several months after discontinuation of amiodarone have been described). Hyperthyroidism occurs more silently with a small number of symptoms: minor unexplained weight loss, decreased antiarrhythmic and/or antianginal effectiveness; mental disorders in elderly patients or even the phenomenon of thyrotoxicosis. The diagnosis is confirmed by identifying a reduced serum TSH level (an ultrasensitive criterion). If hyperthyroidism is detected, amiodarone should be discontinued. Normalization of thyroid function usually occurs within several months after discontinuation of the drug. In this case, clinical symptoms normalize earlier (after 3–4 weeks) than normalization of thyroid hormone levels occurs. Severe cases can be fatal, so urgent medical intervention is required in such cases. Treatment in each individual case is selected individually. If the patient's condition worsens, both due to thyrotoxicosis itself and due to a dangerous imbalance between myocardial oxygen demand and its delivery, it is recommended to immediately begin treatment with corticosteroids (1 mg/kg), continuing it for a long time (3 months), instead the use of synthetic antithyroid drugs, which may not always be effective in this case. Very rarely - syndrome of impaired secretion of antidiuretic hormone.

From the skin: very often - photosensitivity. Often - in case of prolonged use of the drug in high daily doses, grayish or bluish pigmentation of the skin may be observed; After stopping treatment, this pigmentation slowly disappears. Very rarely - during radiation therapy, cases of erythema may occur, there are reports of skin rash, usually of little specificity, isolated cases of exfoliative dermatitis (no connection with the drug has been established); alopecia.

From the central nervous system: often - tremor or other extrapyramidal symptoms; sleep disorders, incl. nightmares. Rarely - sensorimotor, motor and mixed peripheral neuropathies and/or myopathy, usually reversible after discontinuation of the drug. Very rarely - cerebellar ataxia, benign intracranial hypertension (pseudotumor cerebri), headache.

Other: very rarely - vasculitis, epididymitis, several cases of impotence (no connection with the drug has been established), thrombocytopenia, hemolytic anemia, aplastic anemia.

Contraindications

Contraindications to the use of the drug Cordarone are:

Hypersensitivity to iodine, amiodarone or excipients of the drug.

Galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose).

Sick sinus syndrome, sinus bradycardia, sinoatrial block in the absence of an installed artificial pacemaker (pacemaker) in the patient (risk of “stopping” the sinus node).

Atrioventricular block II-III degree, in the absence of an installed artificial pacemaker (pacemaker) in the patient.

Hypokalemia, hypomagnesemia.

Combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including ventricular torsade de pointes (see section “Interaction with other drugs”):

Antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide procainamide); class III antiarrhythmic drugs (dofetilide, ibutilide, bretylium tosylate); sotalol;

Other (non-antiarrhythmic) drugs such as bepridil; vincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular, erythromycin when administered intravenously, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones.

Congenital or acquired prolongation of the QT interval.

Thyroid dysfunction (hypothyroidism, hyperthyroidism).

Interstitial lung disease.

Pregnancy (except in special cases, see section “Use during pregnancy and lactation”).

Lactation period (see section “Use during pregnancy and lactation”).

Age up to 18 years (efficacy and safety have not been established).

With caution: with decompensated or severe chronic (III-IV FC according to the NYHA classification) heart failure, liver failure, bronchial asthma, severe respiratory failure, in elderly patients (high risk of developing severe bradycardia), with first-degree atrioventricular block.

Pregnancy

Currently available clinical information is insufficient to determine the possibility or impossibility of developmental defects in the embryo when amiodarone is used in the first trimester of pregnancy. Since the fetal thyroid gland begins to bind iodine only from the 14th week

pregnancy (amenorrhea), then amiodarone is not expected to affect it if it is used earlier. Excess iodine when using the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in the newborn or even to the formation of a clinically significant goiter.

Due to the effect of the drug Cordarone on the fetal thyroid gland, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit outweighs the risks (in case of life-threatening ventricular arrhythmias).

Breastfeeding period. Amiodarone is excreted into breast milk in significant quantities, so it is contraindicated during breastfeeding (therefore, during this period the drug should be discontinued or breastfeeding should be discontinued).

Interactions with other drugs

Drugs that can cause torsade de pointes or prolong the QT interval

Drugs that can cause ventricular torsade de pointes. Combination therapy with drugs that can cause torsade de pointes is contraindicated, as the risk of developing potentially fatal torsade de pointes increases.

Antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide, procainamide), sotalol, bepridil.

Other (non-antiarrhythmic) drugs: vincamine; some neuroleptics - phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole; terfenadine

Drugs that can prolong the QT interval. Co-administration of amiodarone with drugs that can prolong the QT interval should be based on a careful assessment for each patient of the relationship between the expected benefit and the potential risk (the possibility of an increased risk of developing torsade de pointes). When using such combinations, constant monitoring of the ECG (to detect prolongation of the QT interval), potassium and magnesium levels in the blood is necessary.

Fluoroquinolones, including moxifloxacin, should be avoided in patients taking amiodarone.

Drugs that reduce heart rate or cause automaticity or conduction disorders

Combination therapy with these drugs is not recommended.

Beta-blockers, CCBs that reduce heart rate (verapamil, diltiazem) can cause disturbances in automaticity (development of excessive bradycardia) and conduction.

Drugs that can cause hypokalemia

Not recommended combinations. With laxatives that stimulate intestinal motility and can cause hypokalemia, which increases the risk of developing ventricular “pirouette” tachycardia. When combined with amiodarone, laxatives from other groups should be used.

Combinations that require caution when used. With diuretics that cause hypokalemia (in monotherapy or combinations with other drugs); systemic corticosteroids (GCS, mineralocorticosteroids), tetracosactide; amphotericin B (iv administration).

It is necessary to prevent the development of hypoglycemia, and if it occurs, restore the potassium content in the blood to normal levels, monitor the concentration of electrolytes in the blood and ECG (for possible prolongation of the QT interval); in the event of ventricular “pirouette” tachycardia, antiarrhythmic drugs should not be used (should Ventricular pacing should be started; intravenous administration of magnesium salts is possible).

Preparations for inhalation anesthesia

The possibility of developing the following severe complications in patients receiving amiodarone while receiving general anesthesia has been reported: bradycardia (resistant to atropine), arterial hypotension, conduction disturbances, and decreased cardiac output.

Very rare cases of severe complications from the respiratory system, sometimes fatal, have been observed - acute respiratory distress syndrome in adults, which developed immediately after surgery, the occurrence of which is associated with high oxygen concentrations.

Drugs that slow heart rate

Clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine - risk of developing excessive bradycardia (cumulative effects).

Overdose

When very large doses of the drug Cordarone are taken orally, several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal ventricular “pirouette” tachycardia and liver damage have been described. Atrioventricular conduction may slow down and pre-existing heart failure may worsen.

Treatment should be symptomatic (gastric lavage, use of activated charcoal (if the drug has been taken recently), in other cases symptomatic therapy is carried out: for bradycardia - beta-adrenergic stimulants or installation of a pacemaker, for ventricular “pirouette” tachycardia - intravenous administration of magnesium salts or cardiac stimulation .

Neither amiodarone nor its metabolites are removed by hemodialysis.

There is no specific antidote.

Storage conditions

Store at a temperature not exceeding 30 ºС.

Keep out of the reach of children

Release form

Cordarone - tablets 200 mg.

10 tablets per PVC/Al blister. 3 blisters along with instructions for use in a cardboard box.

Compound

1 tablet of Cordarone contains the active ingredient: amiodarone hydrochloride 200.0 mg.

Excipients: lactose monohydrate, corn starch, magnesium stearate, povidone K90F, colloidal anhydrous silicon dioxide.

Main settings

Name:	CORDARON
ATX code:	C01BD01 -

Cordarone is used in the following cases to relieve an attack:

• paroxysmal tachycardia;
• paroxysmal ventricular tachycardia;
• paroxysmal supraventricular tachycardia with frequent contraction of the ventricles (Wolf-Parkinson-White syndrome);
• paroxysmal atrial fibrillation and its stable form (atrial fibrillation and flutter).

Cordarone is also used to prevent relapses:

• life-threatening ventricular arrhythmias and ventricular fibrillation;
• paroxysmal supraventricular tachycardias, including documented attacks in organic heart diseases;
• documented attacks of sustained paroxysmal supraventricular tachycardia without organic heart disease in case of ineffectiveness of previously used antiarrhythmic drugs or contraindications;
• documented recurrent attacks of sustained paroxysmal supraventricular tachycardia with WPW syndrome;
• atrial fibrillation and atrial flutter.

The injectable form is intended for use to achieve an antiarrhythmic effect and when oral administration is not possible. The drug is used only in hospital settings. Reviews about the drug can be read at the end of the article.

How to use

Tablet form

Loading dose:

• In the hospital: the initial dose, which is divided into several doses, should range from 600-800 mg (maximum = 1200 mg) per day to a total dose of 10 g (usually 5-8 days).
• Outpatient: The initial dose, which is divided into several doses, should be about 600-800 mg per day up to a total dose of 10 g (usually 10-14 days).
• Maintenance dose: 3 mg per kilogram of body weight per day. It can range from 100-400 mg per day with a single dose. It is recommended to use the minimum effective dose based on individual therapeutic results.

Cordarone has a long half-life, so it can be taken every 2nd day (200 mg is given every 2nd day, and 100 mg is recommended daily). You can take breaks 2 times a week).

Injection. Intravenous infusion

Loading dose

For adults - 5 mg per 1 kg of body weight, administered in 250 ml of 5% glucose solution for 20 minutes - 2 hours. You can also administer it two to three times during the day. The infusion rate is adjusted based on the results.

The therapeutic effect appears in the first minutes of administration, gradually decreasing. Maintenance infusion is required.

Maintenance dose

For adults: 10 mg - 20 mg per 1 kg per day (average value - 600 mg - 800 mg per day, maximum dose - 1200 mg per day) in 250 ml of 5% glucose solution for several days. From the very beginning of treatment with infusion, it is necessary to begin transferring to an oral drug.

Intravenous injection

Dose for adults - 5 mg per 1 kg. It is administered for at least 3 minutes. The second injection is performed 15 minutes after the 1st injection, not earlier. To continue treatment, intravenous infusion is used.

Cordarone should not be mixed with other medications in the same syringe.

Composition, release form

Pills

• Amiodarone hydrochloride - 200 mg (active substance);
• Lactose monohydrate 200 mesh. - 71.0 mg;
• Corn starch - 66.0 mg;
• K90F Polyvidone - 6.0 mg;
• Anhydrous colloidal silicon dioxide - 2.4 mg;
• Mg stearate - 4.6 mg per 1 divisible tablet weighing 350.0 mg;

Injection

• Amiodarone hydrochloride 150 mg (active substance);
• Benzyl alcohol - 60 mg;
• Polysorbate 80 - 300 mg;
• Water for injection 3.0 ml.

Beneficial features

Cordarone is a class 3 antiarrhythmic drug that has antiarrhythmic and antianginal effects:

• the drug is able to block a-/b- adrenergic receptors;
• slows down atrial, sinoatrial and nodal conduction without affecting intraventricular conduction;
• increases the refractory period of the accessory ventricular and atrial pathways;
• does not have a negative inotropic effect;
• reduces the contractility of the heart muscle after intravenous administration;
• affects the metabolic processes of thyroid hormones;
• inhibits the transition of T3 hormones to T4 and blocks their uptake by cardiocytes and hepatocytes, which weakens the stimulation of thyroid hormones on the myocardium.

It can be detected in blood plasma for nine months after you stop taking it. The therapeutic effect can be observed 1 week after the start of oral administration.

When administered intravenously, the activity of Cordarone reaches its maximum level 15 minutes after administration and disappears after 4 hours. Despite the short period of elimination of the drug from the body, complete tissue saturation is achieved. In the absence of repetition of injections, the drug is removed gradually. And when renewed, a tissue reserve is formed.

Side effects

Organs of vision:

• deposition of lipofuscin in the corneal epithelium;
• Complaints of “fog” before the eyes rarely appear in very bright light.

Dermatological reactions:

• otosensitization, manifested as erythema on uncovered areas of the skin;
• Rarely, slight pigmentation may appear on uncovered areas of the skin.

Endocrine status:

• Rarely, long-term use may lead to the development of hypothyroidism; very rarely, hyperthyroidism.

The cardiovascular system:

• at high doses of Cordarone, bradycardia may appear, AV conduction may slow down, and arterial hypotension may occur.

Nervous system:

• Rare cases of peripheral neuropathy and tremor may develop.

Gastrointestinal tract and liver:

• nausea;
• heaviness in the epigastrium;
• liver dysfunction.

Respiratory system:

• There have been cases of pneumonitis and alveolitis.

When used parenterally, a feeling of heat, sweating, bronchospasm is possible; in patients with severe heart failure, apnea is possible, intracranial pressure may increase, and a local reaction is phlebitis.

Contraindications

Pills

• hypersensitivity to amiodarone and iodine;
• weak sinus node syndrome (sinus bradycardia, sinoatrial block), with the exception of cases of artificial pacemaker correction;
• violation of atrioventricular and intraventricular conduction;
• combination with drugs that can cause ventricular polymorphic tachycardia of the “pirouette” type;
• dysfunction of the thyroid gland (hypothyroidism or hyperthyroidism);
• heart failure, hypokalemia;
• pregnancy, breastfeeding period;
• age less than 18 years (safety not established);
• simultaneous use of MAO inhibitors;
• interstitial lung diseases.

Injection

• allergy to amiodrone and iodine;
• sinus bradycardia, sinoatrial heart block;
• weak sinus node syndrome (exception - cases of pacemaker correction);
• serious conduction disorders without the use of an artificial pacemaker,
• in complex treatment with drugs that cause ventricular paroxysmal tachycardia;
• dysfunction of the thyroid gland;
• pregnancy, except in serious cases;
• lactation;
• children under 3 years of age.

Interaction with other drugs

The drug can be prescribed together with cardiotonic drugs (for example, digitalis), but there may be a risk of developing bradycardia.

Cordarone is prescribed together with diuretics and anticoagulants.

If you take Cordarone for a long period before surgery, the drug will not have any adverse effects on resuscitation measures and anesthesia.

There are no known cases of interaction of Cordarone with droperidol, chlorprotexene, phenoperidone, dextromoramide, pentobarbital and pancuronium bromide.

It is not recommended to take Verampil and MAO inhibitors together with Cordarone. Cordarone should also not be used together with beta-blockers (with the exception of some severe cases with hemodynamic peculiarities).

Storage conditions and periods

Cordarone solution should be stored at room temperature not exceeding 25°C. Store in the original cardboard box, in a dry place, away from children.

Tablets should be stored at temperatures below 28-30°C.

The drug Cordarone is available only with a doctor's prescription. In the form of a solution for intravenous administration, it is intended for use exclusively in a hospital setting.

Price

Average price for Cordarone tablets 200 mg 30 pcs. in Ukraine and Russia is 128 UAH. and 300 rub. respectively.

The average price of Cordarone solution is 135 UAH and 320 rubles.

Analogues

• Amiocardin;
• Aritmil;
• Vero-Amiodarone;
• Rotaritmil;

Cordarone is an antiarrhythmic drug.

Active substance

Amiodarone hydrochloride.

Release form and composition

Available in the form of tablets and solution for intravenous injection. 1 ampoule contains 3 ml of solution.

Indications for use

Tablets are used to treat the following diseases and pathological conditions:

• atrial fibrillation and atrial flutter;
• life-threatening ventricular arrhythmias, in particular ventricular fibrillation and ventricular tachycardia;
• heart rhythm disturbances in patients with pathology of left ventricular function or coronary heart disease;
• supraventricular paroxysmal tachycardia.

Use is indicated for the prevention of sudden death in patients at high risk:

• having more than 10 ventricular extrasystoles per hour,
  decreased left ventricular ejection fraction,
  in patients after a recent myocardial infarction,
  as well as in patients with clinical manifestations of chronic heart failure.

When treating ventricular arrhythmias, the drug should be used in a hospital setting and under close cardiac monitoring.

Cordarone solution is used in the following cases:

• for cardiac resuscitation in case of cardiac arrest caused by ventricular fibrillation, in case of ineffective defibrillation;
• for stopping attacks of ventricular paroxysmal tachycardia, including those characterized by a high frequency of ventricular contractions;
• to relieve attacks of atrial fibrillation and atrial flutter.

Contraindications

Contraindicated in the following cases:

• with hypersensitivity to amiodarone, iodine or other components of the drug;
• for hypokalemia and hypomagnesemia;
• with AV blockade of the second and third degree;
• with thyroid dysfunction;
• in the presence of congenital or acquired prolongation of the QT interval.

Instructions for use Cordarone (method and dosage)

Pills

The tablets are taken only as prescribed by a doctor orally before meals and washed down with water.

• When treated in a hospital, the initial dose is 600-800 mg, divided into several doses. The maximum dose is 1200 mg per day. Course duration is 5-8 days.
• For outpatient treatment, the initial dose is 600 - 800 mg per day, divided into several doses. The maximum total dose is 10 g. The duration of treatment is 10-14 days.
• Maintenance dose: from 100 to 400 mg per day.

The average single dose is 200 mg, daily dose is 400 mg. The maximum single dose is 400 mg, daily dose is 1200 mg.

Solution

Cordarone for injection is intended to quickly achieve an antiarrhythmic effect, or if it is not possible to take the drug orally.

It is used only in a hospital in an intensive care unit under the control of ECG and blood pressure.

Can only be used in diluted form. Only a 5% dextrose (glucose) solution is used. Administered through a central venous catheter.

In case of severe cardiac arrhythmias, intravenous drip administration is carried out through a central venous catheter. The loading dose is 5 mg per 1 kg of body weight in 250 ml of a 5% dextrose (glucose) solution and is administered, if possible, using an electronic pump over 20-120 minutes.

You can repeat the reception 2-3 times during the day. The rate of administration is adjusted depending on the clinical effect.

Maintenance doses: 10-20 mg/kg/24 hours (usually 600-800 mg, sometimes increasing the dose to 1200 mg over 24 hours) in 250 ml of 5% dextrose (glucose) solution for several days.

It is recommended to begin a gradual transition to oral administration from the first day of infusion. In this case, intravenous fluid management is often contraindicated due to hemodynamic risk. Used only in emergency cases. Dose – 5 mg per 1 kg of body weight.

Side effects

Causes the following side effects:

• moderate bradycardia;
• nausea, vomiting, taste disturbance, loss of appetite, heaviness in the stomach;
• accumulation of microdeposits in the corneal epithelium (usually disappear after withdrawal);
• photosensitivity.

When the drug is administered intravenously, inflammation of the skin often occurs (erythema, pain, superficial phlebitis, thrombophlebitis, infection, pigmentation, and others).

Overdose

Symptoms of an overdose of tablets:

• sinus bradycardia,
• heart failure,
• attacks of ventricular tachycardia,
• paroxysmal tachycardia of the “pirouette” type and liver damage.

Sometimes there is a slowdown in atrioventricular conduction and an increase in previously diagnosed heart failure.

In this case, symptomatic treatment is carried out, including gastric lavage and taking activated charcoal.

Analogues

Analogs by ATC code: Amiodarone, Cardiodarone, Opakrden, Rhythmiodarone, Sedacoron.

Do not decide to change the drug on your own; consult your doctor.

pharmachologic effect

In addition to the antiarrhythmic effect, it has coronary dilation, antianginal, as well as alpha and beta adrenergic blocking effects.

The mechanism of the antiarrhythmic action of Cordarone is due to the ability of the drug to block the ion current in potassium channels and thereby increase the duration of the third phase of the action potential of cardiomyocytes. Reduces heart rate by reducing the automatism of the sinus node, blocks alpha and beta adrenergic receptors, slows down atrial, sinoatrial and AV conduction, and also reduces the excitability of the myocardium of the atria and ventricles.

The use of the drug allows you to achieve the desired effect within 7 days from the start of therapy. Sometimes this period takes from several days to two weeks.

special instructions

• Before starting therapy, an ECG study and a blood test for potassium content should be performed. Hypokalemia must be corrected before starting the drug. Every 3 months during treatment you need to undergo an ECG, monitor transaminase activity and other indicators of liver function.
• Patients with a history of thyroid disease should be examined before starting treatment to identify dysfunctions and diseases of the thyroid gland.
• During therapy, X-ray examination of the lungs and pulmonary function tests should be performed every six months.
• If AV blockade of the second and third degrees, sinoatrial block or double-bundle intraventricular block develops, Cordarone should be discontinued.
• Long-term use of the drug may increase hemodynamic risk when local or general anesthesia is administered.

During pregnancy and breastfeeding

Contraindicated for pregnant and lactating women.

In childhood

Not used in the treatment of children under 18 years of age.

In old age

Use very carefully, as there is a high risk of developing severe bradycardia.

For impaired renal function

For patients with renal failure, it is prescribed in medium doses.

For liver dysfunction

In case of liver failure, it is prescribed with extreme caution.

Drug interactions

• Combination therapy with drugs that cause torsades de pointes is contraindicated.
• When coadministered with drugs that prolong the QT interval, a careful assessment of the expected benefit versus potential risk should be made.
• In combination with diuretics that cause hypokalemia (in monotherapy or combinations with other drugs); systemic corticosteroids (GCS, mineralocorticosteroids), tetracosactide; amphotericin B Cordarone should be used with caution.

Class III antiarrhythmic drug
Drug: CORDARONE

Active substance of the drug: amiodarone
ATX coding: C01BD01
CFG: Antiarrhythmic drug
Registration number: P No. 014833/01-2003
Registration date: 03/12/03
Owner reg. credential: SANOFI WINTHROP INDUSTRIE (France)

Cordarone release form, drug packaging and composition.

Tablets are round, divisible, white or off-white in color, engraved with a symbol in the form of a center and the number “200” on one side; tablets can be easily separated along the break line under normal conditions of use. 1 tab. amiodarone hydrochloride 200 mg
Excipients: lactose monohydrate, corn starch, polyvidone K90F, colloidal anhydrous silicon dioxide, magnesium stearate.
10 pieces. - blisters (3) - cardboard packs.
The solution for intravenous administration is transparent, pale yellow. 1 amp. amiodarone hydrochloride 150 mg
Excipients: benzyl alcohol, polysorbate 80, water, nitrogen.
3 ml - colorless glass ampoules (6) - contour packaging (1) - cardboard boxes.

The description of the drug is based on the officially approved instructions for use.

Pharmacological action Cordarone

Class III antiarrhythmic drug. Has antiarrhythmic and antianginal effects.
The antiarrhythmic effect is due to an increase in phase 3 of the action potential, mainly due to a decrease in potassium current through the channels of the cell membranes of cardiomyocytes and a decrease in the automaticity of the sinus node. The drug non-competitively blocks - and -adrenergic receptors. Slows down sinoatrial, atrial and nodal conduction without affecting intraventricular conduction. Cordarone increases the refractory period and reduces myocardial excitability. Slows down the conduction of excitation and lengthens the refractory period of additional atrioventricular pathways.
The antianginal effect of Cordarone is due to a decrease in oxygen consumption by the myocardium (due to a decrease in heart rate and a decrease in peripheral vascular resistance), non-competitive blockade of - and -adrenergic receptors, an increase in coronary blood flow through a direct effect on the smooth muscles of the arteries, maintaining cardiac output by reducing pressure in the aorta and reducing peripheral resistance.
Cordarone does not have a significant negative inotropic effect and reduces myocardial contractility mainly after intravenous administration.
It affects the exchange 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. Determined in blood plasma for 9 months after stopping its use.
Therapeutic effects are observed 1 week (from several days to 2 weeks) after starting to take the drug orally.
With intravenous administration of Cordarone, its activity reaches a maximum after 15 minutes and disappears approximately 4 hours after administration. Despite the fact that the amount of administered Cordarone in the blood quickly decreases, tissue saturation with the drug is achieved. In the absence of repeated injections, the drug is gradually eliminated. When its administration is resumed or when the drug is prescribed for oral administration, its tissue reserve is formed.

Pharmacokinetics of the drug.

Suction
After oral administration, amiodarone is absorbed slowly (absorption is 30-50%), the rate of absorption is subject to significant fluctuations. Bioavailability after oral administration ranges from 30 to 80% in different patients (on average about 50%). After a single dose of the drug orally, Cmax in blood plasma is achieved within 3-7 hours.
Distribution
Amiodarone has a large Vd. Amiodarone accumulates most in adipose tissue, liver, lungs, spleen and cornea. After a few days, amiodarone is eliminated from the body. Css is achieved within 1 to several months, depending on the individual characteristics of the patient. Binding to blood plasma proteins is 95% (62% to albumin, 33.5% to beta-lipoproteins).
Metabolism
Metabolized in the liver. The main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. Each dose of Cordarone (200 mg) contains 75 mg of iodine; 6 mg of this was determined to be released as free iodine. With prolonged treatment, its concentrations can reach 60-80% of amiodarone concentrations.
Removal
Elimination when taken orally occurs in 2 phases: T1/2 in the -phase - 4-21 hours, T1/2 in the -phase - 25-110 days. After prolonged oral administration, the average T1/2 is 40 days (this is important when choosing a dose, since at least 1 month is required to stabilize the plasma concentration, and complete elimination can last more than 4 months).
After discontinuation of the drug, its complete removal from the body continues for several months. The presence of pharmacodynamic effects of Cordarone should be taken into account for 10 days and up to 1 month after its discontinuation. Amiodarone is excreted in bile and feces. Renal excretion is negligible.

Pharmacokinetics of the drug.

in special clinical cases
Insignificant excretion of the drug in the urine allows the drug to be prescribed in moderate doses for renal failure. Amiodarone and its metabolites are not dialyzable.

Indications for use:

Relief of attacks of ventricular paroxysmal tachycardia;
- relief of attacks of supraventricular paroxysmal tachycardia with a high frequency of ventricular contractions (especially against the background of WPW syndrome);
- relief of paroxysmal and stable forms of atrial fibrillation (atrial fibrillation) and atrial flutter.
Relapse Prevention
- life-threatening ventricular arrhythmias and ventricular fibrillation (treatment should be started in a hospital with careful cardiac monitoring);
- supraventricular paroxysmal tachycardias, incl. documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with organic heart diseases; documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients without organic heart disease, when antiarrhythmic drugs of other classes are not effective or there are contraindications to their use; documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with WPW syndrome;
- atrial fibrillation (atrial fibrillation) and atrial flutter.
- prevention of sudden arrhythmic death in high-risk patients after a recent myocardial infarction, with more than 10 ventricular extrasystoles per hour, clinical manifestations of chronic heart failure and reduced left ventricular ejection fraction (<40%).
Cordarone is especially recommended for patients with organic heart diseases (including coronary artery disease) accompanied by left ventricular dysfunction.
Cordarone for intravenous administration is intended only for use in a hospital in cases where rapid achievement of an antiarrhythmic effect is required or when it is impossible to take the drug orally.

For oral administration
When prescribing the drug in a loading dose, various schemes can be used. When used in a hospital, the initial dose, divided into several doses, ranges from 600-800 mg/day to a maximum of 1200 mg/day (usually for 5-8 days).
For outpatient use, the initial dose, divided into several doses, ranges from 600 mg to 800 mg / day (usually for 10-14 days).
The maintenance dose is determined at the rate of 3 mg/kg body weight per day and can range from 100 mg/day to 400 mg/day when taken once a day. The minimum effective dose should be used. Because Amiodarone has a very long half-life, the drug can be taken every second day (200 mg can be given every second day, and 100 mg is recommended to be taken daily) or taken in breaks (2 days a week).

The loading dose of Cordarone is initially 5-7 mg/kg body weight in 250 ml of a 5% dextrose (glucose) solution for 30-60 minutes. The therapeutic effect of Cordarone appears during the first minutes of administration and disappears gradually, which requires adjustment of the rate of its administration in accordance with the results of treatment.
For maintenance therapy, the drug is prescribed as a continuous or intermittent (2-3 times/day) intravenous infusion in a 5% dextrose (glucose) solution for several days at a dose of up to 1200 mg/day. After IV administration in a loading dose, instead of continuing the IV infusion, it is possible to switch to taking Cordarone orally at a dose of 600-800 mg to 1200 mg/day. From the first day of intravenous administration of Cordarone, it is advisable to begin a gradual transition to taking the drug orally.
When performing intravenous injections, the drug at a dose of 5 mg/kg is administered over at least 3 minutes. Cordarone cannot be taken into the same syringe with other medications!
For intravenous infusion, concentrations below 600 mg/l should not be used. To prepare solutions for intravenous administration, use only a 5% dextrose (glucose) solution.

Side effects of Cordarone:

Solution for intravenous administration
Systemic reactions: feeling of heat, increased sweating, decreased blood pressure (usually moderate and transient); cases of severe arterial hypotension or collapse (have been reported with overdose or too rapid administration), moderate bradycardia (in some cases, especially in elderly patients, severe bradycardia and, in exceptional cases, sinus node arrest, requiring discontinuation of therapy); rarely - proarrhythmic effect. At the beginning of therapy, there is an increase in the activity of hepatic transaminases in the blood serum, which usually remains moderate (1.5-3 times higher than the upper limit of normal (ULN)) and, as a rule, normalizes when the dose is reduced or even spontaneously. If transaminase levels increase significantly, treatment should be discontinued. There are isolated case reports of acute liver failure with high serum levels of liver transaminases and/or jaundice (some with fatal outcome). In isolated (exceptionally rare) cases, anaphylactic shock, benign intracranial hypertension (pseudotumor of the brain), bronchospasm and/or apnea were observed in patients with severe respiratory failure, especially in patients with bronchial asthma. Several cases of acute respiratory distress, mostly associated with interstitial pneumonitis, have been observed.
Local reactions: phlebitis (can be avoided by using a central venous catheter).
For oral administration
From the cardiovascular system: bradycardia (mostly moderate and dose-dependent); in some cases (with sinus node dysfunction, in the elderly) - severe bradycardia; in exceptional cases - sinus block; rarely - conduction disorders (sinoatrial block, AV block of various degrees, intraventricular block); in some cases - the emergence of new arrhythmias or aggravation of existing ones, in some cases - with subsequent cardiac arrest (according to available data, it is impossible to establish a connection with the use of the drug, with the severity of heart damage or with the ineffectiveness of treatment). These effects are observed mainly in cases of combined use of Cordarone with drugs that prolong the period of repolarization of the ventricles of the heart (QTc interval) or in case of electrolyte imbalance.
On the part of the organ of vision: microdeposits of lipofuscin in the cornea of ​​the eye (almost always present) are usually limited to the pupil area, are reversible after discontinuation of the drug, sometimes lead to visual impairment in the form of the appearance of a colored halo in bright light or a feeling of fog; in some cases - neuropathy/optic neuritis (the connection with amiodarone has not been clearly established to date).
Dermatological reactions: photosensitivity; erythema (during radiotherapy); in some cases - rash (usually nonspecific), exfoliative dermatitis (the connection with taking the drug has not been formally established); with prolonged use in high doses - grayish or bluish pigmentation of the skin (slowly disappears after stopping treatment).
From the endocrine system: an increase in the level of T3 in the blood serum (T4 remains normal or slightly reduced) in such cases, in the absence of clinical signs of thyroid dysfunction, discontinuation of the drug is not required); possible development of hypothyroidism (mild weight gain, decreased activity, more pronounced (compared to expected) bradycardia); hyperthyroidism (both during therapy and for several months after stopping the drug). Suspicion of hyperthyroidism may arise from the following mild clinical symptoms: weight loss, development of arrhythmia, angina pectoris, heart failure. The diagnosis is confirmed by a clear decrease in serum TSH. Amiodarone should be discontinued.
From the digestive system: nausea, vomiting, taste disturbances (usually found at the beginning of therapy when used in loading doses and decrease when the dose is reduced); at the beginning of treatment - an isolated increase (1.5-3 times higher than ULN) in the activity of liver transaminases (they decrease with a decrease in the dose of the drug or even spontaneously); in some cases - acute liver dysfunction and/or jaundice (require discontinuation of the drug), fatty hepatosis, cirrhosis. Clinical symptoms and laboratory changes may be minimal (hepatomegaly is possible, increased activity of liver transaminases is increased to 1.5-5 times compared to ULN); Therefore, regular monitoring of liver function is recommended during treatment.
From the respiratory system: in some cases - pneumonitis, fibrosis, pleurisy, bronchiolitis obliterans with pneumonia (sometimes resulting in death), bronchospasm in patients with severe respiratory diseases (especially bronchial asthma), acute respiratory distress syndrome in adults.
From the central nervous system and peripheral nervous system: rarely - sensorimotor peripheral neuropathies and/or myopathies (usually reversible after discontinuation of the drug), extrapyramidal tremor, cerebellar ataxia; in rare cases - benign intracranial hypertension, nightmares.
Allergic reactions: rarely - vasculitis, kidney damage with increased creatinine levels, thrombocytopenia; in some cases - hemolytic anemia, aplastic anemia.
Other: alopecia; in some cases - epididymitis, impotence (no connection with the use of the drug has been established).

Contraindications to the drug:

For oral administration
- SSS (sinus bradycardia, sinoatrial block) except in cases of correction with an artificial pacemaker;
- disturbances of AV and intraventricular conduction (AV blockade of the second and third degree, bundle branch block) in the absence of an artificial pacemaker (pacemaker);
- thyroid dysfunction (hypothyroidism, hyperthyroidism);
- hypokalemia;
- heart failure (in the stage of decompensation);
- simultaneous use of MAO inhibitors;
- interstitial lung diseases;

- pregnancy;
- lactation;

For solution for intravenous administration
- SSS (sinus bradycardia, sinoatrial block) with the exception of patients with an artificial pacemaker (danger of sinus node arrest);
- AV blockade of II and III degrees, intraventricular conduction disorders (blockade of two and three branches of the His bundle); in these cases, IV amiodarone can be used in specialized departments under the cover of an artificial pacemaker (pacemaker);
- acute cardiovascular failure (shock, collapse);
- severe arterial hypotension;
- simultaneous use with drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type;
- dysfunction of the thyroid gland (hypothyroidism, hyperthyroidism);
- pregnancy;
- lactation;
- age under 18 years (efficacy and safety have not been established);
- hypersensitivity to iodine and/or amiodarone.
IV administration is contraindicated in severe pulmonary dysfunction (interstitial lung disease), cardiomyopathy or decompensated heart failure (possible deterioration of the patient's condition).
Use with caution in chronic heart failure, liver failure, bronchial asthma, and in old age (due to the high risk of developing severe bradycardia).

Use during pregnancy and lactation.

During pregnancy, Cordarone is prescribed only for health reasons, because the drug has an effect on the fetal thyroid gland.
Amiodarone is excreted in breast milk in significant quantities, so the drug is contraindicated for use during lactation.

Special instructions for the use of Cordarone.

Before starting and during treatment, it is recommended to conduct an ECG study. Due to the prolongation of the period of repolarization of the ventricles of the heart, the pharmacological action of Cordarone causes certain changes in the ECG: prolongation of the QT interval, QTc, the appearance of U waves is possible. An increase in the QTc interval is permissible by no more than 450 ms or by no more than 25% of the original value. These changes are not a manifestation of the toxic effect of the drug, but require monitoring to adjust the dose and assess the possible proarrhythmogenic effect of Cordarone.
It should be taken into account that in elderly patients there is a more pronounced decrease in heart rate.
If second or third degree AV block, sinoatrial or bifascicular block develops, treatment with Cordarone should be discontinued.
The appearance of shortness of breath or nonproductive cough may be associated with the toxic effect of Cordarone on the lungs. In patients with increasing shortness of breath during exercise, regardless of the deterioration of their general condition (increased fatigue, weight loss, increased body temperature), a chest x-ray should be performed before starting therapy. Respiratory problems are mostly reversible with early discontinuation of amiodarone. Clinical symptoms usually resolve within 3-4 weeks, followed by a slower recovery of radiographic appearance and pulmonary function (several months). Therefore, the possibility of re-evaluating amiodarone therapy and prescribing corticosteroids should be considered.
If blurred vision or decreased visual acuity occurs while taking Cordarone, it is recommended to conduct a full ophthalmological examination, including fundoscopy. Cases of optic neuropathy and/or optic neuritis require a decision on the advisability of using Cordarone.
Cordarone contains iodine (200 mg contains 75 mg of iodine), so it may affect the results of tests for the accumulation of radioactive iodine in the thyroid gland, but does not affect the reliability of the determination of T3, T4 and TSH. Amiodarone may cause thyroid dysfunction, especially in patients with a history of thyroid dysfunction (including a family history). Therefore, before starting treatment, during treatment and several months after the end of treatment, careful clinical and laboratory monitoring should be carried out. If thyroid dysfunction is suspected, serum TSH levels should be measured. When signs of hypothyroidism appear, normalization of thyroid function is usually observed within 1-3 months after cessation of treatment. In life-threatening situations, treatment with amiodarone can be continued, with simultaneous additional administration of levothyroxine. Serum TSH levels serve as a guide for levothyroxine dosage. If signs of hyperthyroidism appear, amiodarone should be discontinued. Normalization of thyroid function usually occurs within several months after discontinuation of the drug. In this case, clinical symptoms normalize before normalization of the level of hormones that reflect the function of the thyroid gland occurs. In severe cases, immediate medical intervention is required. Treatment in each individual case is selected individually and includes antithyroid drugs (which may not always be effective), corticosteroids, and beta-blockers.
Cordarone for intravenous administration is used only in a specialized hospital department under constant monitoring of ECG and blood pressure. In this case, Cordarone should be administered by infusion rather than by injection due to the risk of hemodynamic disturbances (hypotension, acute cardiovascular failure).
IV injections of Cordarone should be performed only in emergency situations, when there are no other therapeutic options, and only in cardiac intensive care units with continuous ECG monitoring.
When administering Cordarone by injection, a dose of approximately 5 mg/kg should be administered over at least 3 minutes. The injection should not be repeated earlier than 15 minutes after the first injection, even if the last one consisted of only one ampoule (irreversible collapse is possible).
Particular caution is required when infusing the drug in cases of arterial hypotension, severe respiratory failure, decompensated cardiomyopathy or severe heart failure.
Patients should avoid prolonged exposure to the sun and UV radiation (or use sunscreen).
Impact on the ability to drive vehicles and operate machinery
Currently, there is no evidence that Cordarone affects the ability to drive vehicles and operate machinery.

Drug overdose:

Symptoms: sinus bradycardia, cardiac arrest, ventricular tachycardia, paroxysmal ventricular tachyarrhythmias of the “pirouette” type, circulatory disorders, liver dysfunction, decreased blood pressure.
Treatment: symptomatic therapy is carried out (gastric lavage, administration of cholestyramine, for bradycardia - beta-adrenergic stimulants or installation of a pacemaker, for tachycardia of the "pirouette" type - intravenous administration of magnesium salts, reducing pacemaker). Amiodarone and its metabolites are not removed by dialysis.
There is no information about overdose with intravenous administration of Cordarone.

Interaction of Cordarone with other drugs.

When taking Cordarone simultaneously with antiarrhythmic drugs (including bepridil, class I A drugs, sotalol), as well as with vincamine, sultopride, erythromycin for intravenous administration, pentamidine for parenteral administration, the risk of developing polymorphic paroxysmal ventricular tachycardia of the “pirouette” type increases. Therefore, these combinations are contraindicated.
Combination therapy with beta-blockers and some calcium channel blockers (verapamil, diltiazem) is not recommended, because Automaticity disorders (manifested by bradycardia) and conduction may develop.
It is not recommended to use Cordarone simultaneously with laxatives (stimulating intestinal motility), which can cause hypokalemia, because the risk of developing ventricular tachycardia of the “pirouette” type increases.
Cordarone should be used with caution simultaneously with drugs that cause hypokalemia (diuretics, systemic corticosteroids and mineralocorticoids, tetracosactide, amphotericin B /for intravenous administration/), because the development of ventricular tachycardia of the “pirouette” type is possible.
When Cordarone is used simultaneously with anticoagulants for oral administration, the risk of bleeding increases (therefore, it is necessary to monitor the level of prothrombin and adjust the dose of anticoagulants).
With the simultaneous use of Cordarone with cardiac glycosides, disturbances in automaticity (manifested by severe bradycardia) and disturbances in atrioventricular conduction may be observed. In addition, it is possible to increase the concentration of digoxin in the blood plasma due to a decrease in its clearance (therefore, it is necessary to monitor the concentration of digoxin in the blood plasma, conduct an ECG and laboratory monitoring, and, if necessary, change

Dosage and method of administration of the drug.

cardiac glycosides).
With the simultaneous use of Cordarone with phenytoin, cyclosporine, flecainide, it is possible to increase the concentration of the latter in the blood plasma (therefore, the concentration of phenytoin, cyclosporine, flecainide in the blood plasma should be monitored and their dose adjusted if necessary).
Cases of bradycardia (resistant to atropine), arterial hypotension, conduction disturbances, and decreased cardiac output have been described in patients taking Cordarone and undergoing general anesthesia.
When using oxygen therapy in the postoperative period in patients receiving Cordarone, rare cases of severe respiratory complications, sometimes resulting in death (acute adult respiratory distress syndrome), have been described.
When used together with simvastatin, the risk of side effects (primarily rhabdomyolysis) may increase due to disruption of the metabolism of simvastatin (if it is necessary to use such a combination, the dose of simvastatin should not exceed 20 mg/day; if the therapeutic effect is not achieved at this dose, you should switch to another lipid-lowering drug).

Terms of sale in pharmacies.

The drug is available with a prescription. The drug in the form of a solution for intravenous administration is intended for use only in a hospital setting.

Terms of storage conditions for the drug Cordarone.

The drug in tablet form should be stored at room temperature (not higher than 30°C). The shelf life of the tablets is 3 years. The drug in the form of a solution for intravenous administration should be stored in a dry place at a temperature not exceeding 25°C. The shelf life of the solution for intravenous administration is 2 years.

Cordarone (active ingredient - amiodarone) is an antiarrhythmic drug from one of the world's leading pharmaceutical corporations, Sanofi Aventis. This drug has been used in clinical practice for more than 50 years and has a truly unique range of pharmacological effects. Cordarone was originally synthesized as a coronary vasodilator for the treatment of angina pectoris. This was in tune with the prevailing ideas at that time about what an ideal antianginal drug should be. However, as it was later found out, the antianginal effect of cordarone is associated not so much with its coronary-dilating effect as with the blockade of myocardial beta-adrenergic receptors. As a result, cordarone is not widely used as an antianginal drug due to poorer tolerability compared to beta blockers and calcium antagonists. Bad luck began: at the end of the 60s of the last century, the antiarrhythmic effect of cordarone was discovered, and the peculiarities of the electrophysiological properties of the drug made it possible to classify it as a new third class of antiarrhythmic drugs at that time. Today, this drug is one of the most commonly and successfully used drugs in the treatment of ventricular and atrial arrhythmias.

The uniqueness of cordarone lies in the fact that in addition to the “standard” properties of class III antiarrhythmic drugs (potassium channel blocking), it accumulates the effects of class I (sodium channel blocking) and class IV antiarrhythmic drugs (calcium channel blocking).

In addition to this, it has the beta-adrenergic blocking effect already mentioned at the beginning of the article. Thus, cordarone is an effective antiarrhythmic agent with a wide range of therapeutic effects. It successfully eliminates ventricular and supraventricular tachyarrhythmias and maintains sinus rhythm in patients with atrial flutter and fibrillation. Cordarone effectively prevents sudden death in patients with heart failure or who have had a myocardial infarction.

Cordarone is available in the form of tablets and solution for intravenous administration. The tablets should be taken before meals with sufficient liquid. The tactics of oral administration of cordarone include a saturation period and a maintenance period. The saturating (loading) dose ranges from 600 to 800 mg per day until a total dose of 10 g is reached (this usually takes 10–14 days). The maintenance dose ranges from 100 to 400 mg per day. Given the long half-life of cordarone, it is not necessary to take it every day (for example, every other day). On average, a single dose of the drug is 200 mg, a daily dose is 400 mg, with a set maximum of 1200 mg. The injection form of cordarone is used only in cases where the speed of implementation of the antiarrhythmic effect is of great importance or if oral administration of the drug is not possible.

Pharmacology

Antiarrhythmic drug. Amiodarone belongs to class III (class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action, because in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (sodium channel blockade), class IV antiarrhythmics (calcium channel blockade) and a non-competitive beta-blocker effect.

In addition to the antiarrhythmic effect, the drug has antianginal, coronary dilation, alpha and beta adrenergic blocking effects.

Antiarrhythmic action:

• an increase in the duration of phase 3 of the action potential of cardiomyocytes, mainly due to blocking the ion current in potassium channels (the effect of class III antiarrhythmics according to the Williams classification);
• decreased 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 AV conduction, more pronounced with tachycardia;
• no changes in ventricular conductivity;
• an increase in refractory periods 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 AV node;
• slowing down conduction and increasing the duration of the refractory period in additional AV conduction bundles.

Other effects:

• lack of negative inotropic effect when taken orally;
• reduction of oxygen consumption by the myocardium due to a moderate decrease in peripheral vascular resistance and heart rate;
• an increase in coronary blood flow due to a direct effect on the smooth muscle of the coronary arteries;
• maintaining cardiac output by reducing pressure in the aorta and reducing peripheral vascular resistance;
• influence on the exchange of thyroid hormones: inhibition of the conversion of T3 to T4 (blockade of thyroxine-5-deiodinase) and blocking the uptake of these hormones by cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium.

After starting to take the drug orally, the therapeutic effects develop on average within a week (from several days to 2 weeks). After stopping its use, amiodarone is detected in the blood plasma for 9 months. The possibility of maintaining the pharmacodynamic effect of amiodarone for 10-30 days after its discontinuation should be taken into account.

Pharmacokinetics

Suction

Bioavailability after oral administration varies from 30% to 80% in different patients (average value about 50%). After a single oral dose of amiodarone, Cmax in blood plasma is reached within 3-7 hours. However, the therapeutic effect usually develops a week after starting the drug (from several days to 2 weeks).

Distribution

Binding to plasma proteins is 95% (62% to albumin, 33.5% to beta-lipoproteins). Amiodarone has a large Vd. Amiodarone is characterized by slow release into tissues and high affinity for them. During the first days of treatment, the drug accumulates in almost all tissues, especially in adipose tissue and, in addition, in the liver, lungs, spleen and cornea.

Metabolism

Amiodarone is metabolized in the liver via isoenzymes CYP3A4 and CYP2C8. Its main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the main compound. Amiodarone and its active metabolite desethylamiodarone in vitro have the ability to inhibit the isoenzymes CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and desethylamiodarone have also demonstrated the ability to inhibit certain transporters, such as P-glycoprotein (P-gp) and organic cation transporter (POK2). In vivo, interactions of amiodarone with substrates of the isoenzymes CYP3A4, CYP2C9, CYP2D6 and P-gp were observed.

Removal

Amiodarone elimination begins within a few days, and achieving equilibrium between the intake and elimination of the drug (achieving C ss) occurs after one to several months, depending on the individual characteristics of the patient. The main route of elimination of amiodarone is the intestine. Amiodarone and its metabolites are not eliminated by hemodialysis. Amiodarone has a long T1/2 with great individual variability (therefore, when selecting a dose, for example, increasing or decreasing it, it should be remembered that at least 1 month is needed to stabilize the new plasma concentration of amiodarone).

Elimination when taken orally occurs in 2 phases: initial T1/2 (first phase) - 4-21 hours, T1/2 in the 2nd phase - 25-110 days. After prolonged oral administration, the average T1/2 is 40 days. After discontinuation of the drug, complete elimination of amiodarone from the body may continue for several months.

Each dose of amiodarone (200 mg) contains 75 mg of iodine. Part of the iodine is released from the drug and is found in the urine in the form of iodide (6 mg per 24 hours with a daily dose of amiodarone 200 mg). Most of the iodine remaining in the drug is excreted through the intestines after passing through the liver, however, with prolonged use of amiodarone, iodine concentrations in the blood can reach 60-80% of amiodarone blood concentrations.

The pharmacokinetic features of the drug explain the use of loading doses, which is aimed at the rapid accumulation of amiodarone in tissues, at which its therapeutic effect is manifested.

Pharmacokinetics in special clinical situations

Due to the insignificant excretion of the drug by the kidneys, no dose adjustment of amiodarone is required in patients with renal failure.

Release form

Tablets are white to off-white in color, round, with a break line on one side, beveled from the edges to the break line and chamfered on both sides, engraved with a heart symbol above the break line and the number “200” below the break line.

Excipients: lactose monohydrate, corn starch, magnesium stearate, povidone K90F, colloidal anhydrous silicon dioxide.

10 pieces. - blisters (3) - cardboard packs.

Dosage

The drug should be taken only as prescribed by a doctor.

Cordarone ® tablets are taken orally before meals and washed down with a sufficient amount of water.

Loading ("saturating") dose: various saturation schemes can be used.

In the hospital: the initial dose, divided into several doses, ranges from 600-800 mg (up to a maximum of 1200 mg) / day until a total dose of 10 g is reached (usually within 5-8 days).

Outpatient: the initial dose, divided into several doses, is from 600 to 800 mg per day until a total dose of 10 g is reached (usually within 10-14 days).

Maintenance dose: may vary in different patients from 100 to 400 mg/day. The minimum effective dose should be used according to the individual therapeutic effect.

Because Cordarone ® has a very large T1/2, it can be taken every other day or take breaks 2 days a week.

The average therapeutic single dose is 200 mg.

The average therapeutic daily dose is 400 mg.

The maximum single dose is 400 mg.

The maximum daily dose is 1200 mg.

Overdose

Symptoms: When ingesting very large doses, several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal ventricular tachycardia of the "pirouette" type and liver damage have been described. Possible slowdown of AV conduction, worsening of existing heart failure.

Treatment: gastric lavage, use of activated charcoal, if the drug has been taken recently; in other cases, symptomatic therapy is carried out: for bradycardia - beta-adrenergic stimulants or installation of a pacemaker; for ventricular tachycardia of the "pirouette" type - intravenous administration of magnesium salts or cardiac stimulation.

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

Interaction

Drugs that can cause torsade de pointes (TdP) or prolong the QT interval

Drugs that can cause torsade de pointes (TdP)

Combination therapy with drugs that can cause ventricular tachycardia of the "pirouette" type is contraindicated, because the risk of developing potentially fatal torsade de pointes (TdP) increases. These include:

• antiarrhythmic drugs: class IA (quinidine, hydroquinidine, disopyramide, procainamide), sotalol, bepridil;
• other (non-antiarrhythmic) drugs such as vincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole; terfenadine

Drugs that can prolong the QT interval

Co-administration of amiodarone with drugs that can prolong the QT interval should be based on a careful assessment for each patient of the ratio of expected benefit and potential risk (the possibility of an increased risk of developing torsade de pointes); when using such combinations, it is necessary to constantly monitor the ECG of patients (for detection of QT interval prolongation), potassium and magnesium content in the blood.

Fluoroquinolones, including moxifloxacin, should be avoided in patients taking amiodarone.

Drugs that slow the heart rate or cause problems with automaticity or conduction

Combination therapy with these drugs is not recommended.

Beta-blockers, slow calcium channel blockers that reduce heart rate (verapamil, diltiazem) can cause disturbances in automaticity (development of excessive bradycardia) and conduction.

Drugs that can cause hypokalemia

• with laxatives that stimulate intestinal motility, which can cause hypokalemia, which increases the risk of developing torsades de pointes. When combined with amiodarone, laxatives from other groups should be used.

Combinations requiring caution when using

• with diuretics that cause hypokalemia (in monotherapy or in combination with other drugs);
• with systemic corticosteroids (glucocorticoids, mineralocorticoids), tetracosactide;
• with amphotericin B (iv administration).

It is necessary to prevent the development of hypoglycemia, and if it occurs, restore the potassium content in the blood to normal levels, monitor the concentration of electrolytes in the blood and ECG (for possible prolongation of the QT interval), and in the event of ventricular tachycardia of the “pirouette” type, antiarrhythmic drugs should not be used (ventricular pacing should be started; intravenous administration of magnesium salts is possible).

Preparations for inhalation anesthesia

The possibility of developing the following severe complications in patients taking amiodarone during general anesthesia has been reported: bradycardia (resistant to atropine), decreased blood pressure, conduction disturbances, decreased cardiac output.

Very rare cases of severe complications from the respiratory system, sometimes fatal, have been observed (acute respiratory distress syndrome in adults, which developed immediately after surgery, and the occurrence of which is associated with high oxygen concentrations).

Drugs that reduce heart rate (clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine

Risk of developing excessive bradycardia (cumulative effects).

Effect of amiodarone on other drugs

Amiodarone and/or its metabolite desethylamiodarone inhibit the isoenzymes CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein and may increase the systemic exposure of drugs that are their substrates. Due to the long half-life of amiodarone, this interaction can be observed even several months after stopping its use.

Drugs that are P-gp substrates

Amiodarone is a P-gp inhibitor. It is expected that its combined use with drugs that are P-gp substrates will lead to increased systemic exposure of the latter.

Cardiac glycosides (digitalis preparations)

Possibility of disturbances in automaticity (severe bradycardia) and atrioventricular conduction. In addition, when combining 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 combining digoxin with amiodarone, it is necessary to determine the concentration of digoxin in the blood and monitor possible clinical and electrocardiographic manifestations of digitalis intoxication. Digoxin dosages may need to be reduced.

Dabigatran

Caution should be exercised when amiodarone is used concomitantly with dabigatran due to the risk of bleeding. The dose of dabigatran may need to be adjusted in accordance with the instructions in its instructions for use.

Medicines that are substrates of the CYP2C9 isoenzyme

Amiodarone increases the blood concentration of drugs that are substrates of the CYP2C9 isoenzyme, such as warfarin or phenytoin due to inhibition of cytochrome P450 2C9.

Warfarin

When warfarin is combined with amiodarone, the effects of the indirect anticoagulant may be enhanced, which increases the risk of bleeding. Prothrombin time should be monitored more frequently (by determining MHO) and anticoagulant doses adjusted, both during treatment with amiodarone and after discontinuation of its use.

Phenytoin

When combining phenytoin with amiodarone, an overdose of phenytoin may develop, which can lead to the appearance of neurological symptoms; Clinical monitoring and reduction of the dose of phenytoin is necessary at the first signs of overdose; it is advisable to determine the concentration of phenytoin in the blood plasma.

Medicines that are substrates of the CYP2D6 isoenzyme

Flecainide

Amiodarone increases plasma concentrations of flecainide due to inhibition of the CYP2D6 isoenzyme, which requires adjustment of flecainide doses.

Medicines that are substrates of the CYP3A4 isoenzyme

When amiodarone, an inhibitor of the CYP3A4 isoenzyme, is combined with these drugs, their plasma concentrations may increase, which may lead to increased toxicity and/or increased pharmacodynamic effects and may require a reduction in their doses. Such medicines are listed below.

Cyclosporine

The combination of cyclosporine with amiodarone may increase plasma concentrations of cyclosporine; dose adjustment is necessary.

Fentanyl

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

HMG-CoA reductase inhibitors (statins) (simvastatin, atorvastatin and lovastatin)

Increased risk of statin muscle toxicity when used concomitantly with amiodarone. The use of statins that are not metabolized by the CYP3A4 isoenzyme is recommended.

Other drugs metabolized by CYP3A4: lidocaine (risk of sinus bradycardia and neurological symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (risk of increased side effects), midazolam (risk of psychomotor effects), triazolam, dihydroergotamine, ergotamine, colchicine .

Amiodarone inhibits CYP2D6 and CYP3A4 and may theoretically increase plasma concentrations of dextromethorphan.

Clopidogrel

Clopidogrel is an inactive thienopyrimidine drug that is metabolized in the liver to form active metabolites. There is a possible interaction between clopidogrel and amiodarone, which may lead to a decrease in the effectiveness of clopidogrel.

Effect of other drugs on amiodarone

Inhibitors of CYP3A4 and CYP2C8 isoenzymes may have the potential to inhibit the metabolism of amiodarone and increase its concentration in the blood and, accordingly, its pharmacodynamic and side effects.

It is recommended to avoid CYP3A4 inhibitors (eg, grapefruit juice and certain drugs such as cimetidine and HIV protease inhibitors (including indinavir) during therapy with amiodarone. HIV protease inhibitors, when used concomitantly with amiodarone, may increase amiodarone concentrations in blood.

Inducers of the CYP3A4 isoenzyme

Rifampicin

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

Preparations of St. John's wort

St. John's wort is a potent inducer of the CYP3A4 isoenzyme. In this regard, it is theoretically possible to reduce the plasma concentration of amiodarone and reduce its effect (clinical data are not available).

Side effects

The frequency of side effects was determined according to the WHO classification: very common (≥10%); often (≥1%,<10); нечасто (≥0.1%, <1%); редко (≥0.01%, <0.1%); очень редко, включая отдельные сообщения (<0.01%); частота неизвестна (по имеющимся данным частоту определить нельзя).

From the cardiovascular system: often – bradycardia, usually moderate, the severity of which depends on the dose of the drug; infrequently - conduction disturbance (sinoatrial block, AV block of various degrees), arrhythmogenic effect (there are reports of the emergence of new arrhythmias or aggravation of existing ones, in some cases - with subsequent cardiac arrest); Based on the available data, it is impossible to determine whether the occurrence of these rhythm disturbances is caused by the action of the drug Cordarone ®, the severity of cardiovascular pathology, or is a consequence of treatment ineffectiveness. These effects are observed mainly in cases of use of the drug Cordarone ® in conjunction with drugs that prolong the period of repolarization of the ventricles of the heart (QT interval) or in cases of disturbances in the content of electrolytes in the blood.

Very rarely - severe bradycardia or, in exceptional cases, sinus node arrest, which were observed in some patients (patients with sinus node dysfunction and elderly patients), vasculitis; frequency unknown - progression of chronic heart failure (with long-term use), ventricular tachycardia of the "pirouette" type.

From the digestive system: very often - nausea, vomiting, dysgeusia (dulling or loss of taste), usually occurring when taking a loading dose and disappearing after its reduction.

From the liver and biliary tract: very often - isolated increase in transaminase activity in the blood serum, usually moderate (1.5-3 times higher than normal values; decreases with dose reduction or spontaneously); often - acute liver damage with increased transaminase activity and/or jaundice, including the development of liver failure, sometimes fatal; very rarely - chronic liver diseases (pseudoalcoholic hepatitis, cirrhosis), sometimes fatal. Even with a moderate increase in transaminase activity in the blood, observed after treatment lasting more than 6 months, chronic liver damage should be suspected.

From the respiratory system: often - pulmonary toxicity, sometimes fatal (alveolar/interstitial pneumonitis or fibrosis, pleurisy, bronchiolitis obliterans with pneumonia). Although these changes can lead to the development of pulmonary fibrosis, they are largely reversible with early discontinuation of amiodarone and with or without the use of corticosteroids. Clinical manifestations usually disappear within 3-4 weeks. Recovery of the X-ray picture and lung function occurs more slowly (several months). The appearance of severe shortness of breath or a dry cough in a patient taking amiodarone, either accompanied or not accompanied by a deterioration in the general condition (increased fatigue, loss of body weight, increase in body temperature), requires a chest x-ray and, if necessary, discontinuation of the drug.

Very rarely - bronchospasm (in patients with severe respiratory failure, especially in patients with bronchial asthma), acute respiratory distress syndrome (sometimes fatal and sometimes immediately after surgery; possible interaction with high oxygen concentrations is expected).

Frequency unknown - pulmonary hemorrhage.

On the part of the organ of vision: very often - microdeposits in the corneal epithelium, consisting of complex lipids, including lipofuscin, they are usually limited to the pupil area and do not require cessation of treatment and disappear after discontinuation of the drug, sometimes they can cause visual impairment in the form of a colored halo or blurriness contours in bright light; very rarely - optic neuritis/optic neuropathy (no relationship with amiodarone has been established to date; however, since optic neuritis can lead to blindness, if blurred vision or decreased visual acuity occurs while taking Cordarone ®, a full ophthalmological examination is recommended, including fundoscopy, and if optic neuritis is detected, stop taking the drug).

From the endocrine system: often - hypothyroidism (weight gain, chilliness, apathy, decreased activity, drowsiness, excessive bradycardia compared to the expected effect of amiodarone). The diagnosis is confirmed by identifying an elevated serum TSH level (using an ultrasensitive TSH test); normalization of thyroid function is usually observed within 1-3 months after cessation of treatment; in life-threatening situations, treatment with amiodarone can be continued with simultaneous additional administration of L-thyroxine under the control of serum TSH levels.

Hyperthyroidism is also common, sometimes fatal, and may occur during and after treatment (cases of hyperthyroidism developing several months after discontinuation of amiodarone have been described). Hyperthyroidism occurs more silently with a small number of symptoms: minor unexplained weight loss, decreased antiarrhythmic and/or antianginal effectiveness; mental disorders in elderly patients or even the phenomenon of thyrotoxicosis. The diagnosis is confirmed by identifying a reduced serum TSH level (using an ultrasensitive TSH test). If hyperthyroidism is detected, amiodarone should be discontinued. Normalization of thyroid function usually occurs within several months after discontinuation of the drug. In this case, clinical symptoms normalize earlier (after 3-4 weeks) than normalization of thyroid hormone levels occurs. Severe cases can be fatal, so urgent medical intervention is required in such cases. Treatment in each individual case is selected individually. If the patient's condition worsens both due to thyrotoxicosis itself and due to a dangerous imbalance between the myocardial oxygen demand and its delivery, it is recommended to immediately begin treatment: the use of antithyroid drugs (which may not always be effective in this case), treatment with corticosteroids ( 1 mg/kg), which lasts quite a long time (3 months), beta-blockers.

Very rarely - syndrome of impaired secretion of ADH.

From the skin and subcutaneous tissues: very often - photosensitivity; often (in case of prolonged use of the drug in high daily doses) - grayish or bluish pigmentation of the skin (after stopping treatment, this pigmentation slowly disappears); very rarely - erythema (during radiation therapy), skin rash (usually unspecific), alopecia, exfoliative dermatitis, alopecia; frequency unknown - urticaria.

From the nervous system: often - tremor or other extrapyramidal symptoms, sleep disturbances, nightmares; uncommon - sensorimotor peripheral neuropathies and/or myopathy (usually reversible within a few months after discontinuation of the drug, but sometimes not completely); very rarely - cerebellar ataxia, benign intracranial hypertension (pseudotumor cerebri), headache.

From the genital organs and mammary gland: very rarely - epididymitis, impotence.

From the hematopoietic system: very rarely - thrombocytopenia, hemolytic anemia, aplastic anemia.

Allergic reactions: frequency unknown - angioedema (Quincke's edema).

Laboratory and instrumental data: very rarely - an increase in the concentration of creatinine in the blood serum.

General disorders: frequency unknown - granuloma formation, including bone marrow granuloma.

Indications

Relapse Prevention

• life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be started in the hospital with careful cardiac monitoring).
• supraventricular paroxysmal tachycardia:
• documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with organic heart disease;
• documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients without organic heart disease, when antiarrhythmic drugs of other classes are not effective or there are contraindications to their use;
• documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome.
• atrial fibrillation (atrial fibrillation) and atrial flutter.

Prevention of sudden arrhythmic death in high-risk patients

• patients after a recent myocardial infarction with more than 10 ventricular extrasystoles per hour, clinical manifestations of chronic heart failure and a reduced left ventricular ejection fraction (less than 40%).

Cordarone ® can be used in the treatment of arrhythmias in patients with coronary artery disease and/or impaired left ventricular function.

Contraindications

• SSS (sinus bradycardia, sinoatrial block), except in cases of their correction with an artificial pacemaker (danger of “stopping” the sinus node);
• AV blockade of II and III degrees in the absence of an artificial pacemaker (pacemaker);
• hypokalemia, hypomagnesemia;
• interstitial lung disease;
• thyroid dysfunction (hypothyroidism, hyperthyroidism);
• congenital or acquired prolongation of the QT interval;
• combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including torsades de pointes: class I A antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, procainamide); class III antiarrhythmic drugs (dofetilide, ibutilide, bretylium tosylate); sotalol; other (non-antiarrhythmic) drugs such as bepridil; vincamine; some neuroleptics phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; antibiotics of the macrolide group (in particular erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine for parenteral administration; difemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones;
• age under 18 years (efficacy and safety have not been established);
• pregnancy;
• lactation period;
• lactose intolerance (lactase deficiency), glucose-galactose malabsorption syndrome (the drug contains lactose);
• hypersensitivity to iodine, amiodarone or excipients of the drug.

Use with caution in decompensated or severe chronic (III-IV functional class according to the NYHA classification) heart failure, liver failure, bronchial asthma, severe respiratory failure, in elderly patients (high risk of developing severe bradycardia), with 1st degree AV blockade .

Features of application

Use during pregnancy and breastfeeding

Pregnancy

Currently available clinical information is insufficient to determine the possibility or impossibility of developmental defects in the embryo when using amiodarone in the first trimester of pregnancy.

Since the fetal thyroid gland begins to bind iodine only from the 14th week of pregnancy (amenorrhea), amiodarone is not expected to affect it if it is used earlier. Excess iodine when using the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in the newborn or even to the formation of a clinically significant goiter.

Due to the effect of the drug on the fetal thyroid gland, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit outweighs the risks (in case of life-threatening ventricular arrhythmias).

Breastfeeding period

Amiodarone is excreted into breast milk in significant quantities, so it is contraindicated during breastfeeding (during this period the drug should be discontinued or breastfeeding should be stopped).

Use for liver dysfunction

Use with caution in case of liver failure.

Use for renal impairment

Insignificant excretion of the drug in the urine allows the drug to be prescribed in moderate doses for renal failure. Amiodarone and its metabolites are not dialyzable.

Use in children

Contraindication: children and adolescents under 18 years of age (efficacy and safety have not been established).

special instructions

Because Side effects of amiodarone are dose-dependent, and patients should be treated with the lowest effective doses to minimize their occurrence.

Patients should be warned to avoid exposure to direct sunlight or to take protective measures (eg, use of sunscreen, wearing appropriate clothing) during treatment.

Treatment monitoring

Before starting amiodarone, it is recommended to conduct an ECG study and determine the potassium level in the blood. Hypokalemia should be corrected before starting amiodarone. During treatment, it is necessary to regularly monitor ECG (every 3 months) and transaminase activity and other indicators of liver function.

In addition, due to the fact that amiodarone can cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, before taking amiodarone, clinical and laboratory (serum TSH concentration determined using an ultrasensitive TSH test) examination should be performed for the subject of identifying dysfunctions and diseases of the thyroid gland. During treatment with amiodarone and for several months after its cessation, the patient should be regularly monitored for clinical or laboratory signs of changes in thyroid function. If thyroid dysfunction is suspected, it is necessary to determine the concentration of TSH in the blood serum (using an ultrasensitive TSH test).

In patients receiving long-term treatment for arrhythmias, increased rates of ventricular defibrillation and/or increased thresholds for pacemaker or implanted defibrillator response have been reported, which may reduce the effectiveness of these devices. Therefore, before starting or during treatment with amiodarone, their correct functioning should be checked regularly.

Regardless of the presence or absence of pulmonary symptoms during treatment with amiodarone, it is recommended to conduct an X-ray examination of the lungs and pulmonary function tests every 6 months.

The appearance of shortness of breath or a dry cough, either isolated or accompanied by a deterioration in general condition (fatigue, weight loss, fever), may indicate pulmonary toxicity such as interstitial pneumonitis, the suspicion of which requires X-ray examination of the lungs and pulmonary function tests. samples

Due to the prolongation of the period of repolarization of the ventricles of the heart, the pharmacological effect of the drug Cordarone ® causes certain ECG changes: prolongation of the QT interval, QT s (corrected), the appearance of U waves is possible. An increase in the QT interval s is permissible by no more than 450 ms or by no more than 25% of the original quantities. These changes are not a manifestation of the toxic effect of the drug, but require monitoring to adjust the dose and evaluate the possible proarrhythmogenic effect of the drug Cordarone ® .

If II and III degree AV block, sinoatrial block or double-bundle intraventricular block develops, treatment should be discontinued. If 1st degree AV block occurs, monitoring should be intensified.

Although the occurrence of arrhythmias or worsening of existing arrhythmias, sometimes fatal, has been reported, the proarrhythmogenic effect of amiodarone is mild (less pronounced than most antiarrhythmic drugs) and usually occurs in the context of factors prolonging the QT interval, such as interactions with other drugs and/or in case of disturbances in the content of electrolytes in the blood. Despite the ability of amiodarone to prolong the QT interval, it has shown little activity in inducing torsade de pointes (TdP).

If vision is blurred or visual acuity is reduced, an immediate ophthalmological examination, including fundus examination, is necessary. With the development of neuropathy or optic neuritis caused by amiodarone, the drug must be discontinued due to the risk of blindness.

Since Cordarone ® contains iodine, its use may interfere with the absorption of radioactive iodine and distort the results of a radioisotope study of the thyroid gland, however, taking the drug does not affect the reliability of determining the content of T3, T4 and TSH in the blood plasma. Amiodarone inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increased serum free T4 concentrations with slightly decreased or even normal serum free T3 concentrations) in clinically euthyroid patients, which is not the cause to discontinue amiodarone.

The development of hypothyroidism can be suspected when the following clinical signs, usually mild, appear: weight gain, cold intolerance, decreased activity, excessive bradycardia.

Before surgery, the anesthesiologist should be informed that the patient is taking Cordarone ®.

Long-term treatment with Cordarone ® may increase the hemodynamic risk inherent in local or general anesthesia. This particularly applies to its bradycardic and hypotensive effects, decreased cardiac output and conduction disturbances.

In addition, in rare cases, acute respiratory distress syndrome was observed in patients taking Cordarone ® immediately after surgery. These patients require careful monitoring during mechanical ventilation.

Careful monitoring of liver function tests (determining transaminase activity) is recommended before starting to take the drug Cordarone ® and regularly during treatment with the drug. Acute liver dysfunction (including hepatocellular failure or liver failure, sometimes fatal) and chronic liver damage may occur when taking the drug Cordarone ® . Therefore, treatment with amiodarone should be discontinued when transaminase activity increases to 3 times the ULN.

Clinical and laboratory signs of chronic liver failure when taking amiodarone orally can be minimally expressed (hepatomegaly, increased transaminase activity 5 times the ULN) and reversible after discontinuation of the drug, but cases of death with liver damage have been reported.

Impact on the ability to drive vehicles and operate machinery

Based on safety data, there is no evidence that amiodarone impairs the ability to drive or engage in other potentially hazardous activities. However, as a precautionary measure, it is advisable for patients with paroxysms of severe rhythm disturbances during treatment with Cordarone ® to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.