Acute bronchitis in children clinical recommendations

In this article, you can read the instructions for use of the drug. Cordaron. Presented reviews of visitors to the site – the consumers of this medicine, as well as the opinions of medical specialists on the use of Cordaron in their practice. A big request to add your feedback on the drug more actively: the medicine helped or did not help to get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Analogs of Cordaron in the presence of available structural analogues. Use for the treatment of arrhythmias and atrial and ventricular fibrillation in adults, children, as well as during pregnancy and lactation. The composition of the drug.

Cordaron – antiarrhythmic drug. Amiodarone (active ingredient of the drug Cordarone) belongs to class 3 (class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action,

In addition to the antiarrhythmic effect of the drug, there are antianginal, coronary expanding, alpha and beta adrenoceptor blocking effects.

The antiarrhythmic effect of the drug is due to the increase in the duration of the 3 phase potential of the action of cardiomyocytes, mainly due to blocking the ionic current in the potassium channels (the effect of class 3 antiarrhythms according to Vaughan-Williams classification); a decrease in the automatism of the sinus node, leading to a decrease in heart rate; noncompetitive blockade of alpha and beta adrenoreceptors; slowing of sinoatrial, atrial, and AV conduction, more pronounced with tachycardia; no change in ventricular conduction; an increase in refractory periods and a decrease in atrial and ventricular myocardial excitability, as well as an increase in the refractory period of the AV node; by slowing the conduction and increasing the duration of the refractory period in additional bundles of AV conduction.

In addition, Cordaron has the following properties: the absence of a negative inotropic effect when taken orally; decrease in oxygen consumption by the myocardium due to a moderate decrease in OPSS and heart rate; an increase in coronary blood flow due to a direct effect on the smooth muscles of the coronary arteries; maintaining cardiac output by reducing pressure in the aorta and reducing OPS; effect on thyroid hormone metabolism: inhibition of the conversion of T3 to T4 (blocking thyroxin-5-deiodinase) and blocking the capture of these hormones by cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium.

After starting the drug inside, therapeutic effects develop on average in a week (from several days to 2 weeks). After discontinuation of its administration, amiodarone is determined in the blood plasma for 9 months. The possibility of preserving the pharmacodynamic action of amiodarone for 10–30 days after its withdrawal should be taken into account.

Composition

Amiodarone hydrochloride + excipients.

Pharmacokinetics

Bioavailability after oral administration in different patients ranges from 30% to 80% (average value of about 50%). Amiodarone is characterized by a slow entry into the tissue and high affinity for it. 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. The equilibrium state is reached after from 1 to several months, depending on the individual characteristics of the patient. The features of the pharmacokinetics of the drug due to the use of loading doses, which is aimed at the rapid achievement of the required level of penetration into the tissue, which manifests the therapeutic effect of amiodarone. Metabolized in the liver. The main metabolite, dezethylamidarone, is pharmacologically active and may enhance the antiarrhythmic effect of the parent compound. Removal of amiodarone begins after a few days. Excreted mainly through the intestines.

Indications

  • life-threatening ventricular arrhythmias and ventricular fibrillation of the heart (treatment should be started in the hospital with careful cardiac monitoring);
  • supraventricular paroxysmal tachycardia, in

Prevention of sudden arrhythmic death in patients at high risk:

    patients after recent myocardial infarction, having more than 10 ventricular extrasystoles in 1 h, clinical manifestations of chronic heart failure and a reduced left ventricular ejection fraction (

When prescribing the drug in a loading dose, various schemes can be used.

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

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

The maintenance dose may vary in different patients from 100 mg per day to 400 mg per day. The minimum effective dose should be applied in accordance with the individual therapeutic effect.

The average therapeutic single dose is 200 mg. The average therapeutic daily dose is 400 mg.

The maximum single dose – 400 mg. The maximum daily dose is 1200 mg.

Cordarone for intravenous administration is intended for use in cases where it is necessary to quickly achieve an antiarrhythmic effect, or if it is impossible to use the drug inside.

With the exception of urgent clinical situations, the drug should be used only in a hospital in the intensive care unit under the constant supervision of ECG and blood pressure.

With the / in the introduction of Cordarone can not be mixed with other drugs or simultaneously enter other drugs through the same venous access. The drug should be administered only in diluted form. For dilution Cordarone should use only 5% dextrose (glucose) solution. Due to the characteristics of the medicinal form of the drug, it is not recommended to use the concentration of the infusion solution, which is less than that obtained by diluting 2 ampoules in 500 ml of 5% dextrose (glucose).

To avoid reactions at the injection site, Cordarone should be administered through the central venous catheter, except in cases of cardio-resuscitation in ventricular fibrillation resistant to cardioversion, when in the absence of central venous access the drug can be injected into peripheral veins (the largest peripheral vein with maximum blood flow).

Severe cardiac arrhythmias, in cases where it is impossible to take the drug inside (except for cases of cardio-resuscitation with cardiac arrest caused by ventricular fibrillation resistant to cardioversion)

The drug is administered intravenously drip (dropper) through the central venous catheter.

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

Maintenance doses: 10–20 mg / kg / 24 h (usually 600–800 mg, but may be increased to 1200 mg within 24 h) in 250 ml of a 5% dextrose solution (glucose) within a few days. From the first day of infusion, you should begin a gradual transition to the intake of Cordarone orally at a dose of 600 mg (3 tablets) per day. The dose can be increased to 800-1000 mg (4-5 tablets) per day.

Cardioreanimation in cardiac arrest resistant cardioversion caused by ventricular fibrillation

The drug is administered intravenously bolus. The first dose is 300 mg (or 5 mg / kg) in 20 ml of 5% dextrose (glucose) solution. If fibrillation is not stopped, then the additional introduction of Cordarone in / in the jet 150 mg dose (or

Side effect

  • moderate dose dependent bradycardia
  • conduction disturbance (sinoatrial blockade, AV blockade of various degrees)
  • arrhythmogenic effect (there are reports of new arrhythmias or exacerbation of existing ones, in some cases with subsequent cardiac arrest; these effects are observed mainly in cases of Cordarone use together with drugs that prolong the QTc interval or electrolyte imbalance; in the light of the available data to determine whether the occurrence of these rhythm disturbances is caused by Cordarone, or is associated with the severity of cardiac pathology, or is a consequence of treatment failure)
  • severe bradycardia or, in exceptional cases, sinus node arrest (mainly in patients with sinus node dysfunction and elderly patients)
  • progression of heart failure (with prolonged use)
  • nausea, vomiting
  • loss of appetite
  • dullness or loss of taste
  • feeling of heaviness in the epigastrium (occurs mainly at the beginning of treatment, disappear after dose reduction)
  • interstitial or alveolar pneumonitis
  • bronchiolitis obliterans with pneumonia (sometimes fatal)
  • pleurisy
  • bronchospasm (in patients with severe respiratory failure, especially in patients with bronchial asthma)
  • acute respiratory distress syndrome (sometimes fatal and sometimes immediately after surgical interventions; the possibility of interaction with high doses of oxygen is assumed)
  • pulmonary hemorrhage
  • microcorrelations in the corneal epithelium consisting of complex lipids, including lipofuscin
  • optic neuritis
  • hypothyroidism (weight gain, chilliness, apathy, decreased activity, drowsiness, excessive bradycardia compared with the expected effect of amiodarone)
  • hyperthyroidism, which is possible during and after treatment (cases of hyperthyroidism that developed several months after discontinuation of amiodarone were described)
  • photosensitization
  • grayish or bluish pigmentation of the skin (after cessation of treatment, this pigmentation slowly disappears)
  • erythema (during radiation therapy)
  • skin rash (usually not very specific)
  • alopecia
  • exfoliative dermatitis (connection with taking the drug has not been established)
  • tremor or other extrapyramidal symptoms
  • sleep disorders
  • nightmares
  • myopathy
  • headache
  • thrombocytopenia, hemolytic anemia, aplastic anemia
  • vasculitis
  • several cases of impotence (connection with the drug has not been established).

Contraindications

  • SSS (sinus bradycardia, sinoatrial block), except in cases of correction by an artificial pacemaker (danger "stop" sinus node);
  • AV block 2 and 3 degrees in the absence of a permanent artificial pacemaker (pacemaker);
  • two- and three-bundle blockade in the absence of a 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 polymorphic ventricular tachycardia type "pirouette": Class 1 A antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, procainamide); Class 3 antiarrhythmic drugs (dofetilide, ibutilide, bretilium tosylate); sotalol; other (non-antiarrhythmic) drugs such as bepridil; Vincamine; some phenothiazines neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, flufenazine), benzamides (amisulpride, sultopride, sulpiride, tiaprid, veralipride), butyrophenones (droperidol, calidi, I, I, I, I, I), butyrophenones (Droperidol, I, I, I, I, I, I, I, I, I, I, I, I, I, I, I, I, I, I will use my name). cisapride; tricyclic antidepressants; antibiotics of the macrolide group (in particular, erythromycin with a / in the introduction, spiramycin); azoles; antimalarials (quinine, chloroquine, mefloquine, halofantrine); pentamidine when administered parenterally; difemanil methyl sulfate; mizolastine; astemizole, terfenadine; fluoroquinolones;
  • children and adolescents under 18 years of age (efficacy and safety have not been established);
  • pregnancy;
  • lactation period;
  • hypersensitivity to iodine and / or amiodarone.

Use during pregnancy and lactation

Cordarone is contraindicated during pregnancy and lactation (breastfeeding).

Currently available clinical information is insufficient to determine the degree of risk of developmental malformations in the embryo when using Cordarone in the 1st trimester of pregnancy.

Since the thyroid gland of the fetus begins to bind iodine only from the 14th week of pregnancy (amenorrhea), it is not expected that amiodarone will affect it if it is used earlier. Excess iodine in the application of the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in the newborn or even the formation of a clinically significant goiter. Due to the effect of the drug on the thyroid gland of the fetus, Cordarone is contraindicated for use during pregnancy, with the exception of special cases of vital indications (for life-threatening ventricular arrhythmias).

Amiodarone is excreted in breast milk in significant quantities, so if you need to use the drug during lactation, breastfeeding should be canceled.

Use in elderly patients

Caution should be used in elderly patients (high risk of developing severe bradycardia).

Use in children

Contraindicated in children and adolescents under the age of 18 years (efficacy and safety have not been established).

special instructions

Side effects of Cordarone are dose-dependent, so to minimize the possibility of their occurrence, the drug should be used in the minimum effective dose.

During treatment, patients should avoid exposure to direct sunlight or take protective measures (for example, applying sunscreen, wearing appropriate clothing).

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

In addition, due to the fact that Cordarone can cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, a clinical and laboratory (TSH content) examination should be conducted before taking amiodarone to detect abnormalities in function and disease of the thyroid gland. During treatment with amiodarone and for several months after it is discontinued, regular examinations are required to identify clinical or laboratory signs of changes in thyroid function. If you suspect a dysfunction of the thyroid gland, it is necessary to determine the serum TSH level.

Regardless of the presence or absence during pulmonary symptomatic treatment with amiodarone, it is recommended to perform an x-ray examination of the lungs and pulmonary functional tests every 6 months.

In patients receiving long-term treatment for rhythm disturbances, an increase in the frequency of ventricular fibrillation and / or an increase in the threshold of the pacemaker or implanted defibrillator has been reported, which may reduce their effectiveness. Therefore, before starting or during treatment with Cordaron, you should regularly check the correct functioning of these devices.

The appearance of shortness of breath or dry cough, both isolated and accompanied by deterioration of the general condition, indicates the possibility of pulmonary toxicity, such as interstitial pneumopathy, the suspicion of the development of which requires an x-ray examination of the lung and pulmonary functional samples.

Due to the lengthening of the period of repolarization of the ventricles of the heart, the pharmacological action of Cordaron causes certain changes on the ECG: lengthening of the QT, QTc (corrected) interval, U waves may appear. The QTc interval can be increased by no more than 450 ms or by more than 25% of the original value. These changes are not a manifestation of the toxic effect of the drug, but require monitoring for dose adjustment and evaluation of the possible proarrhythmic effect of Cordarone.

With the development of AV block 2 and 3 degrees, sinoatrial block or double-diplex intraventricular block, the treatment should be stopped. At occurrence of an AV blockade of the 1st degree, strengthening of clinical control is required.

Although the occurrence of arrhythmias or aggravation of existing rhythm disturbances was noted, the proarrhythmic effect of amiodarone is weak, less than with most antiarrhythmic drugs, and usually manifests itself in combination with certain drugs or electrolyte imbalance.

If blurred vision or a decrease in visual acuity is necessary to conduct an ophthalmologic examination, including examination of the fundus. With the development of neuropathy or neuritis of the optic nerve caused by amiodarone, the drug must be canceled due to the risk of developing blindness.

Since Cordarone contains iodine, its use may distort the results of a radioisotope study of the thyroid gland, but does not affect the accuracy of the determination of the content of T3, T4 and TSH in blood plasma.

Before surgery, the anesthesiologist should be informed that the patient is receiving Cordarone. Prolonged treatment with Cordarone may increase the hemodynamic risk inherent in local or general anesthesia. This is especially true of its bradycardic and hypotensive effects, reduction of cardiac output and conduction disorders.

In addition, in patients receiving Cordarone, in rare cases, immediately after surgery, acute respiratory distress syndrome was noted. With mechanical ventilation, such patients require careful monitoring.

Influence on ability to drive motor transport and control mechanisms

During the period of treatment with Cordaron, one should refrain from driving a car and engaging in potentially hazardous activities that require increased concentration and psychomotor reactions.

Drug interaction

Cordarone is contraindicated in combination therapy with drugs that can cause polymorphic ventricular tachycardia of the type "pirouette",

  • antiarrhythmic drugs: class 1A (quinidine, hydroquinidine, disopyramide, procainamide), class 3 (dofetilide, ibutilide, bretylium tosylate), sotalol;
  • other (non-antiarrhythmic) drugs such as bepridil; Vincamine; Some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, flufenazine), benzamides (amisulpride, sultopride, sulpiride, tiapridide, veralipride), butyrophenones (droperidol, I), I used to go to a hotel, I’m not too young; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with a / in the introduction, spiramycin); azoles; antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine when administered parenterally; difemanil methyl sulfate; mizolastine; astemizole; terfenadine; fluoroquinolones (in particular moxifloxacin).
  • with beta-blockers, with slow calcium channel blockers that slow down heart rate (verapamil, diltiazem),

Careful handling is required.

With drugs that can cause hypokalemia:

  • diuretics that cause hypokalemia (in monotherapy or combination);
  • Amphotericin B (IV);
  • glucocorticosteroids (GCS) for systemic use;
  • tetracosactide.

Increased risk of ventricular arrhythmias, especially ventricular tachycardia type "pirouette" (hypokalemia is a predisposing factor). It is necessary to control the content of electrolytes in the blood, if necessary – correction of hypokalemia, constant clinical observation and ECG monitoring. In the case of ventricular tachycardia type "pirouette" antiarrhythmic drugs should not be used (ventricular pacing should be initiated, possibly with / in the introduction of magnesium salts).

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

With indirect anticoagulants

Amiodarone increases the concentration of warfarin by inhibiting the CYP2C9 isoenzyme. With the combination of warfarin with amiodarone may increase the effects of indirect anticoagulant, which increases the risk of bleeding. Prothrombin time (INR) should be monitored more frequently and the dose of anticoagulant should be adjusted both during treatment with amiodarone and after it is canceled.

With cardiac glycosides (digitalis preparations)

Possible violations of automatism (marked bradycardia) and atrioventricular conduction. In addition, the combination of digoxin with amiodarone may increase the concentration of digoxin in the blood plasma (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 the possible clinical and ECG manifestations of digitalis intoxication. May require reduced doses of digoxin.

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

With phenytoin (and, by extrapolation, with fosfenitoin)

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

With drugs metabolized by CYP3A4 isoenzyme

Acute bronchitis in children clinical recommendations

When combined with amiodarone, an inhibitor of the CYP3A4 isoenzyme, these drugs may increase their plasma concentrations, which can lead to an increase in their toxicity and / or increased pharmacodynamic effects and may require a decrease in the dose of such drugs:

  • cyclosporine: possible increase in the concentration of cyclosporine in the blood plasma, associated with a decrease in the metabolism of the drug in the liver, which can increase the nephrotoxic effect of cyclosporine. It is necessary to determine the concentration of cyclosporine in the blood, monitor kidney function and correct the dosage regimen of cyclosporine during the period of treatment with amiodarone and after discontinuation of the drug.
  • fentanyl: when combined with amiodarone, it is possible to enhance the pharmacodynamic effects of fentanyl and increase the risk of its toxic effects.
  • other drugs that are metabolized with the participation of CYP3A4: lidocaine (risk of developing sinus bradycardia and neurological symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (risk of increasing its side effects), midazolam (risk of developing psychomotor effects), triazolam, dihydroergotamine, ergotham, ergotham, ergothamine, ergothamine, ergothamine, risk of developing psychomotor effects, triazolam, dihydroergotamine, ergothamos, risk of developing psychomotor effects including simvastatin (increased risk of muscle toxicity, rhabdomyolysis, and therefore the dose of simvastatin should not exceed 20 mg per day, if it is ineffective, you should switch to taking a different statin that does not metabolize using CYP3A4).

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

With clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, takrin, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine

There is a risk of excessive bradycardia (cumulative effects).

With cimetidine, grapefruit juice

There is a slowdown in the metabolism of amiodarone and an increase in its plasma concentrations, possibly an increase in the pharmacodynamic and side effects of amiodarone.

With drugs for inhalation anesthesia

It was reported about the possibility of the development of the following serious complications in patients receiving amiodarone during anesthesia: bradycardia (resistant to atropine), hypotension, conduction disorders, reduction of cardiac output. There were very rare cases of severe complications of the respiratory system (acute adult respiratory distress syndrome), sometimes fatal, which developed immediately after surgery, the occurrence of which is associated with high concentrations of oxygen.

With radioactive iodine

Amiodarone contains iodine in its composition and therefore may interfere with the absorption of radioactive iodine, which may distort the results of a radioisotope study of the thyroid gland.

Rifampicin is a potent inducer of CYP3A4; therefore, when used together with amiodarone, plasma concentrations of amiodarone and dezethylamidarone may decrease.

With Hypericum

Hypericum is a powerful inducer of CYP3A4. In this regard, it is theoretically possible to decrease the plasma concentration of amiodarone and decrease its effect (there are no clinical data).

With HIV protease inhibitors (in

HIV protease inhibitors are inhibitors of CYP3A4, therefore, when used concurrently with amiodarone, they can increase the concentration of amiodarone in the blood.

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

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

Analogs of the drug Cordaron

Structural analogues of the active substance:

  • Amiodarone;
  • Amiokordin;
  • Vero Amiodarone;
  • Cardiodarone;
  • Opacordain;
  • Rhythtiodarone;
  • Sedacoron.

Analogs for pharmacological group (antiarrhythmic drugs):

  • Adenocore;
  • Allapinin;
  • Asparkam;
  • Bretilate;
  • Hypertonplant (Gnafalin);
  • Dinexane;
  • Difenin;
  • Cardiodarone;
  • Quinidine Durules;
  • Lidocaine;
  • Moracizin;
  • Multak;
  • Neo Gilurithmal;
  • Nibentan;
  • Novocainamide;
  • Pamaton;
  • Panangin;
  • Procainamid Eskom;
  • Propanorm;
  • Propafenone;
  • Profenan;
  • Ritalmex;
  • Rhythtiodarone;
  • Ritmodan;
  • Ritmonorm;
  • Sedacoron;
  • Trimecain;
  • Etatsizin;
  • Etmozin.
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