Cordarone, tablets 200 mg 30 pcs

Cordarone is an antiarrhythmic drug.

Amiodarone belongs to class III antiarrhythmic drugs (class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action because in addition to properties of class III antiarrhythmic agents (potassium channel blockade) it has effects of class I antiarrhythmic agents (sodium channel blockade), class IV antiarrhythmic agents (calcium channel blockade) and noncompetitive beta blocking action.

In addition to antiarrhythmic action, it has antianginal, coronary dilator, alpha- and beta-adrenoblocking effects.
Antiarrhythmic properties:

– increase the duration of the 3rd phase of the action potential of cardiomyocytes, mainly due to the blocking of the ionic current in potassium channels (effect of antiarrhythmic agent of class III according to Williams classification);
– reduction of sinus node automatism, resulting in decreased heart rate;
– non-competitive blockade of alpha- and beta-adrenergic receptors;
– Slowing-down of sinoatrial, atrial and atrioventricular conduction, more pronounced in tachycardia;
– Absence of changes in ventricular conduction;
– increased refractory periods and decreased excitability of atrial and ventricular myocardium, as well as increased refractory period of atrioventricular node;
– delayed conduction and increased duration of refractory period in additional bundles of atrial-ventricular conduction.

Other effects:

– decreased myocardial oxygen consumption by moderately reducing total peripheral resistance and heart rate, and decreasing myocardial contractility through beta-adrenoblocking action;
– Increase of coronary blood flow due to direct effect on coronary artery tone;
– Preservation of cardiac output, despite some decrease of myocardial contractility, due to the decrease of total peripheral resistance and aortic pressure;
– Effect on thyroid hormone metabolism: Inhibition of the conversion of T3 to T4 (blockade of thyroxine-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.
– restoration of cardiac activity in cardiac arrest caused by ventricular fibrillation resistant to cardioversion.

Indications

Stenocardia, paroxysmal rhythm disorders: supraventricular tachycardia, atrial fibrillation, sinus tachycardia, extrasystoles (supraventricular and ventricular).

Active ingredient

Amiodarone

Composition

1 tablet contains amiodarone 200 mg.

How to take, the dosage

During the first 8-14 days 1 tablet 2-3 times a day; thereafter 1 tablet a day – after every 5 days of use a break of 2 days).

In children: in the initial daily dose of 8-10 mg/kg for 8-14 days, then the maintenance dose is changed to a maintenance dose

.

Interaction

– With drugs that can cause polymorphic ventricular tachycardia of “pirouette” type (torsade de pointes) (when combined with amiodarone the risk of potentially fatal ventricular tachycardia of “pirouette” type increases):
– antiarrhythmic agents: class IA (quinidine, hydroquinidine, disopyramide, procainamide), class III (dofetilide, ibutilide, brettilia tozilate), sotalol;
– other (non antiarrhythmic) drugs, such as bepridil; vincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, thiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindol, pimozide; tricyclic antidepressants; cisapride macrolide antibiotics (erythromycin when given intravenously, spiramycin); azoles; antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine when given parenterally; difemanil methylsulfate; misolastine; astemizole; terfenadine; fluoroquinolones (particularly moxifloxacin).

Not recommended combinations

– With beta-adrenoblockers, with “slow” calcium channel blockers that slow the heart rate (verapamil, diltiazem), because there is a risk of developing disorders of automaticity (marked bradycardia) and conduction.
– With laxatives stimulating intestinal peristalsis that may cause hypokalemia, which increases the risk of pirouette-type ventricular tachycardia. When combining with amiodarone, laxatives of other groups should be used.
Combinations requiring caution when using
– With drugs that may cause hypokalemia:
– diuretics that cause hypokalemia (in monotherapy or combination);
– amphotericin B (w/v);
– systemic glucocorticosteroids;
– tetracosactide.

An 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, correction of hypokalemia and constant clinical and electrocardiographic monitoring of the patient. In case of development of ventricular tachycardia of “pirouette” type, antiarrhythmic drugs should not be used (ventricular pacing should be initiated, intravenous administration of magnesium salts is possible).
– With procainamide (see “Interaction. Contraindicated combinations”

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

– With indirect-acting anticoagulants
Amiodarone increases warfarin concentrations by inhibiting cytochrome P450 2C9. When combining warfarin with amiodarone, the effects of indirect anticoagulant may be enhanced, which increases the risk of bleeding. Prothrombin time (INR) should be monitored more frequently and anticoagulant doses should be adjusted both during treatment with amiodarone and after its withdrawal.
– With cardiac glycosides (foxglove preparations)

The possibility of automatic disorders (marked bradycardia) and atrial-ventricular conduction. In addition, when combining digoxin with amiodarone, the concentration of digoxin in blood plasma may increase (due to decreased clearance). Therefore, when combining digoxin with amiodarone, it is necessary to determine digoxin concentration in blood and monitor possible clinical and electrocardiographic manifestations of digoxin intoxication. Doses of digoxin may need to be decreased.

– With esmolol
Disorders of contractility, automaticity and conduction (suppression of compensatory responses of the sympathetic nervous system). Clinical and ECG monitoring is required.

– With phenytoin (and, by extrapolation, with fosphenytoin)
Amiodarone may increase plasma concentrations of phenytoin by inhibiting cytochrome P450 2C9, so combining phenytoin with amiodarone may result in phenytoin overdose, which may lead to neurologic symptoms; clinical monitoring is necessary and, at the first sign of overdose, reduction of the dose of phenytoin, and determination of plasma phenytoin concentrations is desirable.

– With flecainide
Amiodarone increases plasma concentrations of flecainide due to inhibition of CYP 2D6 cytochrome. Due to this fact, correction of flecainide doses is required.

– With drugs metabolized by cytochrome P450 3A4
When combining amiodarone, a CYP 3A4 inhibitor, with these drugs, their plasma concentrations may increase, which may lead to increased toxicity and/or increased pharmacodynamic effects and may require reduction of their doses. These drugs are listed below.

– Cyclosporine
There may be increased plasma levels of cyclosporine associated with decreased metabolism of the drug in the liver, which may increase the nephrotoxic effects of cyclosporine. Blood cyclosporine concentrations should be determined, renal function should be monitored, and the dosing regimen of cyclosporine should be adjusted during amiodarone treatment and after drug withdrawal.

– Fentanyl
Combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of its toxic effects.
– Other drugs metabolized by CYP 3A4: lidocaine (risk of sinus bradycardia and neurologic symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (risk of increased side effects), midazolam (risk of psychomotor effects), triazolam, dihydroergotamine, ergotamine, simvastatin and other statins, metabolized with CYP 3A4 (increased risk of muscle toxicity, rhabdomyolysis, therefore the dose of simvastatin should not exceed 20 mg per day, if ineffective, switch to another statin that is not metabolized with CYP 3A4).

– With orlistat
Risk of decreased plasma concentrations of amiodarone and its active metabolite. Clinical and, if necessary, ECG monitoring is necessary.

– 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
Slows down the metabolism of amiodarone and increases its plasma concentrations and may increase the pharmacodynamic and side effects of amiodarone.

– With drugs for inhalation anesthesia
The following severe complications have been reported in patients receiving amiodarone when they receive general anesthesia: bradycardia (resistant to atropine administration), arterial hypotension, conduction disturbances, and decreased cardiac output.
There have been very rare cases of severe complications of the respiratory system (acute adult respiratory distress syndrome), sometimes fatal, which developed immediately after surgical intervention, the occurrence of which is associated with high oxygen concentrations.

– With radioactive iodine
Amiodarone contains iodine and therefore can interfere with radioactive iodine absorption, which can distort the results of radioiodine thyroid examination.

– With rifampicin
Rifampicin is a potent inducer of CYP3A4 and may decrease plasma concentrations of amiodarone and desethylamiodarone when combined with amiodarone.

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

– With HIV protease inhibitors (including indinavir)
HIV protease inhibitors are CYP3A4 inhibitors. Concomitant use with amiodarone may increase the blood concentration of amiodarone.

– 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 decreased efficacy of clopidogrel.

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

Special Instructions

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

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

Treatment monitoring

Before starting amiodarone, an ECG study and determination of blood potassium levels are recommended. Hypokalemia should be corrected before starting amiodarone. During treatment, ECG should be regularly monitored (every 3 months) and transaminase levels and other liver function parameters should be monitored.

In addition, because amiodarone may cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, clinical and laboratory (TTG) examinations for thyroid dysfunction and disease should be performed before taking amiodarone. During treatment with amiodarone and for several months after discontinuation, the patient should be evaluated regularly for clinical or laboratory signs of altered thyroid function. If thyroid dysfunction is suspected, serum TSH levels should be determined.
Regardless of the presence or absence of pulmonary symptoms during amiodarone treatment, lung X-ray examination and pulmonary functional tests are recommended every 6 months.

In patients receiving long-term treatment for rhythm disturbances there have been reported cases of increased rate of ventricular fibrillation and/or increased threshold for pacemaker or implanted defibrillator activation, which may reduce their effectiveness. Therefore, proper functioning of these devices should be regularly checked before or during treatment with amiodarone.
The occurrence of dyspnea or dry cough, either isolated or accompanied by a deterioration in general condition, should indicate the possibility of pulmonary toxicity such as interstitial pneumopathy, suspected of which requires radiological examination of the lungs and pulmonary function tests.

Due to the prolongation of the period of ventricular repolarization of the heart, the pharmacological action of Cordarone causes certain ECG changes: prolongation of the QT interval, QTc interval (corrected), the appearance of U waves is possible. It is acceptable to increase the Q-Tc interval not more than 450 ms or not more than 25% of the original value. These changes are not manifestation of toxic action of the drug, but require monitoring for dose adjustment and assessment of possible proarrhythmogenic effect of Cordarone.

If atrioventricular block of degree II and III, sinoatrial block or double-ventricular intraventricular block develops, treatment should be discontinued. If grade I atrioventricular block occurs, monitoring should be intensified.

While the occurrence of arrhythmias or aggravation of existing rhythm disturbances has been noted, the proarrhythmogenic effect of amiodarone is mild, less than that of most antiarrhythmic drugs, and is usually seen in combination with certain medications or with electrolyte imbalances.

In case of blurred vision or decreased visual acuity, an ophthalmologic examination, including fundus examination, should be performed. If amiodarone-induced neuropathy or optic neuritis develops, the drug should be withdrawn because of the risk of blindness.

Because Cordarone contains iodine, its use may distort the results of radioisotopic examination of the thyroid gland, but does not affect the reliability of determining the plasma T3, T4 and TSH content.

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 particularly true for its bradycardic and hypotensive effects, decreased cardiac output, and conduction disturbances.

In addition, acute respiratory distress syndrome has been noted in patients receiving Cordarone in rare cases immediately after surgical intervention. Close monitoring is required in these patients when ventilating them.

Influence on driving and other machinery

During treatment with Cordarone one should refrain from driving and engaging in potentially dangerous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

Hypersensitivity, sinus bradycardia, AV blockade, thyroid disorders, pregnancy.

Side effects

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

Overdose

A few cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal pirouette tachycardia and liver damage have been described when very high doses are taken orally. Deceleration of atrioventricular conduction and aggravation of pre-existing heart failure are possible.

The treatment should be symptomatic (gastric lavage, administration of activated charcoal (if the drug was taken recently), otherwise symptomatic therapy is used: in bradycardia – beta-adrenergic pacemakers or pacemaker placement, in “pirouette” tachycardia – IV magnesium salts or cardiostimulation. Neither amiodarone nor its metabolites are removed by hemodialysis.
There is no specific antidote.

Similarities

Amiodarone