Cordarone, pills 200mg, 30pcs

Composition

1 tablet contains amiodarone 200 mg

Pharmacological action

Cordarone is an antiarrhythmic drug.

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-blocking action.

In addition to its antiarrhythmic action, it has antianginal, coronary dilating, alpha-and beta-blocking effects. Antiarrhythmic properties: − an increase in the duration of the 3rd phase of the cardiomyocyte action potential, mainly due to blocking the ion current in the potassium channels (the effect of an antiarrhythmic agent of Class III according to the Williams classification)− – a decrease in the automatism 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 in tachycardia;− absence of changes in ventricular conduction− – increase in refractory periods and decrease in excitability of the atrial and ventricular myocardium, as well as an increase in the refractory period of the atrioventricular node;− slowing down and increasing the duration of the refractory period in additional bundles of atrioventricular conduction.

Other effects:

− reduced consumption of oxygen by the myocardium at the expense of a moderate decrease in total peripheral resistance and heart rate and reduce myocardial contractility through beta-adrenoblockers action;- an increase in coronary blood flow due to direct effects on the tone of the coronary arteries;- preservation of cardiac output, despite some reduction of myocardial contractility by reducing total peripheral resistance and aortic pressure;- the impact on the metabolism of thyroid hormones: the inhibition of the conversion of T 3 to T 4 (thyroxine blockade-5-deiodinase) and blocking the capture of these hormones cardiocyte and hepatocytes, leading to the weakening of the stimulating effect of thyroid hormones on the myocardium. – restoration of cardiac activity in cardiac arrest caused by ventricular fibrillation resistant to cardioversion.

Indications

Angina pectoris, paroxysmal rhythm disorders: supraventricular tachycardia, atrial fibrillation, sinus tachycardia, extrasystole (supraventricular and ventricular).

Contraindications

Hypersensitivity, sinus bradycardia, AV block, thyroid diseases, pregnancy.

Side effects

Nausea, vomiting, constipation, bradycardia, euphoria, tremor, hypo – and hyperthyroidism, phlebitis, neuropathy, photosensitization, headache, fatigue, allergic reactions.

Interaction

– With drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type (torsade de pointes) (when combined with amiodarone, the risk of developing potentially fatal ventricular tachycardia of the “pirouette” type increases): − antiarrhythmic drugs: Class IA (quinidine, hydroquinidine, disopyramide, procainamide), Class III (dofetilide, ibutilide, bretilia 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), sertindol, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (intravenous erythromycin, spiramycin); azoles; antimalarial agents (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine with parenteral use; difemanyl methylsulfate; mizolastine; astemizole; terfenadine; fluoroquinolones (in particular moxifloxacin).

Not recommended combinations

– With beta-blockers, with blockers of “slow” calcium channels that slow down the heart rate (verapamil, diltiazem), as there is a risk of developing violations of automatism (pronounced bradycardia) and conduction. – With laxatives that stimulate intestinal motility, which can cause hypokalemia, which increases the risk of developing ventricular tachycardia of the “pirouette” type. When combined with amiodarone, laxatives of other groups should be used. Combinations that require caution when used – With drugs that can cause hypokalemia: – diuretics that cause hypokalemia (alone or in combination);- amphotericin B (iv);- systemic glucocorticosteroids;- tetracosactide.

Increased risk of ventricular arrhythmias, especially ventricular tachycardia of the “pirouette” type (hypokalemia is a predisposing factor). It is necessary to monitor the level of electrolytes in the blood, if necessary, correct hypokalemia and constant clinical and electrocardiographic monitoring of the patient. In case of development of ventricular tachycardia of the “pirouette” type, antiarrhythmic drugs should not be used (ventricular pacing should be started, intravenous use of magnesium salts is possible). – With procainamide (see ” Interaction. Contraindicated combinations”Amiodarone may increase the plasma concentration of procainamide and its metabolite N-acetylprokainamide, which may increase the risk of side effects of procainamide.

– With indirect anticoagulants, Amiodarone increases the concentration of warfarin by inhibiting cytochrome P450 2C9. When warfarin is combined with amiodarone, the effects of an indirect anticoagulant may increase, which increases the risk of bleeding. Prothrombin time (INR) should be monitored more frequently and anticoagulant doses adjusted both during and after amiodarone treatment. – With cardiac glycosides (digitalis preparations)

The possibility of occurrence of violations of automatism (severe 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 possible clinical and electrocardiographic manifestations of digitalis intoxication. It may be necessary to reduce the dose of digoxin.

– With esmololomnarusheniya contractility, automatism and conductivity (suppression of compensatory reactions of the sympathetic nervous system). Clinical and ECG monitoring is required.

– With phenytoin (and, by extrapolation, with phosphenytoin)Amiodarone can increase plasma concentrations of phenytoin by inhibiting cytochrome P4502C9, therefore, when combined with phenytoin and amiodarone, an overdose of phenytoin may develop, which may 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 blood plasma.

– With flecainide, Amiodarone increases the plasma concentration of flecainide by inhibiting cytochrome CYP 2D6. Therefore, correction of flecainide doses is required.

– With drugs metabolized by cytochrome P4503A4 When combined with amiodarone, a CYP 3A4 inhibitor, with these drugs, their plasma concentrations may increase, which may lead to an increase in their toxicity and/or increased pharmacodynamic effects and may require a reduction in their doses. These medications are listed below.

– Cyclosporine: It is possible to increase the level of cyclosporine in blood plasma, associated with a decrease in the metabolism of the drug in the liver, which may increase the nephrotoxic effect of cyclosporine. It is necessary to determine the concentration of cyclosporine in the blood, monitor renal function and adjust the dosage regimen of cyclosporine during treatment with amiodarone and after discontinuation of the drug.

– Fentanyl combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects. – Other drugs metabolized by CYP 3 A 4: 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, simvastatin and other statins metabolized by CYP 3 A 4 (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 another statin that is not metabolized by CYP 3 and 4).

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

– With clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine Risk of excessive bradycardia (cumulative effects).

– With cimetidine, grapefruit juice, slowing down the metabolism of amiodarone and increasing its plasma concentrations, it is possible to increase the pharmacodynamic and side effects of amiodarone.

– With drugs for inhaled anesthesia, the possibility of developing the following serious complications in patients receiving amiodarone, when they receive general anesthesia: bradycardia (resistant to the introduction of atropine), arterial hypotension, conduction disorders, decreased cardiac output.There were very rare cases of severe respiratory complications (acute respiratory distress syndrome of adults), sometimes fatal, which developed immediately after surgery, the occurrence of which is associated with high oxygen concentrations.

– 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, and when co-administered with amiodarone, it can reduce plasma concentrations of amiodarone and desethylamiodarone.

– With St. John’s wort preparations, St. John’s wort is a powerful inducer of CYP3A4. In this regard, it is theoretically possible to reduce the plasma concentration of amiodarone and reduce its effect (no clinical data available)..

– With HIV protease inhibitors( including indinavir)HIV protease inhibitors are inhibitors of CYP3A4. When used concomitantly with amiodarone, they can increase the concentration of amiodarone in the blood.

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

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

How to take, course of use and dosage

in the first 8-14 days,1 table 2-3 times a day; in the future-1 table. per day — every 5 days of reception should be a break for 2 days).

Children: at an initial daily dose of 8-10 mg / kg for 8-14 days, then switch to a maintenance dose

Overdose

Several cases of sinus bradycardia, cardiac arrest, ventricular tachycardia, paroxysmal pirouette tachycardia, and liver damage have been reported with very high oral doses. It is possible to slow down the atrioventricular conduction, increase the pre-existing heart failure.

Treatment should be symptomatic (gastric lavage, use of activated charcoal (if the drug is taken recently), in other cases, symptomatic therapy is carried out: for bradycardia – beta-adrenostimulants or pacemaker installation, for tachycardia of the “pirouette” type – intravenous use of magnesium salts or pacing. Neither amiodarone nor its metabolites are removed by hemodialysis. There is no specific antidote.

Special instructions

Since the side effects of amiodarone are dose-dependent, patients should be treated with the minimum effective doses to minimize the possibility of their occurrence.

Patients should be warned to avoid direct sunlight during treatment or to take protective measures (for example, applying sunscreen, wearing appropriate clothing).

Treatment monitoring

Before taking amiodarone, it is recommended to conduct an ECG study and determine the level of potassium in the blood. Hypokalemia should be corrected before starting amiodarone. During treatment, it is necessary to regularly monitor the ECG (every 3 months) and the level of transaminases 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 diseases, a clinical and laboratory (TSH) examination should be performed before taking amiodarone to detect thyroid dysfunction and diseases. During treatment with amiodarone and for several months after its discontinuation, the patient should be regularly evaluated for clinical or laboratory signs of changes in thyroid function. If you suspect a violation of thyroid function, it is necessary to determine the level of TSH in the blood serum. 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.

In patients receiving long-term treatment for rhythm disorders, cases of increased frequency of ventricular fibrillation and/or an increase in the response threshold of a pacemaker or implanted defibrillator have been reported, which may reduce their effectiveness. Therefore, before starting or during amiodarone treatment, you should regularly check the correct functioning of these devices. The occurrence of shortness of breath or dry cough, either isolated or accompanied by deterioration of the general condition, should indicate the possibility of pulmonary toxicity, such as interstitial pneumopathy, the suspected development of which requires an X-ray examination of the lungs and pulmonary function tests.

Due to the prolongation of the period of repolarization of the ventricles of the heart, the pharmacological effect of Cordarone causes certain ECG changes: prolongation of the QT interval, QTc (corrected), the appearance of U waves is possible. It is permissible to increase the Q-Tc interval by no more than 450 ms or no 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 proarrhythmogenic effect of Cordarone.

If grade II and III atrioventricular block, sinoatrial block, or double-bundle intraventricular block develops, treatment should be discontinued. If grade I atrioventricular block occurs, follow-up should be increased.

Although the occurrence of arrhythmia or aggravation of existing rhythm disorders has been noted, the proarrhythmogenic effect of amiodarone is weak, less than that of most antiarrhythmic drugs, and usually manifests itself in combination with certain medications or in cases of electrolyte disturbances.

If you have blurry vision or reduced visual acuity, you should perform an ophthalmological examination, including an examination of the fundus. If amiodarone causes neuropathy or optic neuritis, the drug should be discontinued 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 it does not affect the reliability of determining 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 associated with local or general anesthesia. This is especially true for its bradycardic and hypotensive effects, reduced cardiac output, and conduction disturbances.

In addition, patients who received Cordarone in rare cases immediately after surgery noted acute respiratory distress syndrome. With artificial ventilation, such patients need careful monitoring.

Influence on the ability to drive a car and other mechanisms

During treatment with Cordarone, you should refrain from driving a car and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Pills.

Storage conditions

In a place protected from light, at a temperature not exceeding 15 °C.

Active ingredient

Amiodarone

Conditions of release from pharmacies

By prescription

Dosage form

Tablets