Cordarone pills 200 mg 30 pcs
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Active ingredients
Amiodarone
Release form
Pills
Composition
Active ingredient: Amiodarone (Amiodarone) Concentration of the active substance (mg): 200
Pharmacological effect
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 (blockade of potassium channels), it has the effects of class I antiarrhythmics (sodium channel blockade), class IV antiarrhythmics (calcium channel blockade) and noncompetitive beta-adrenoceptor blocking action. beta-adrenergic blocking effects. Antiarrhythmic action: - an increase in the duration of the 3 phase action potential of cardiomyocytes, mainly due to the blocking of the ion current in the potassium channels ( the effect of class III antiarrhythmics according to Williams classification); - reduction of sinus node automatism, leading to a decrease in heart rate; - noncompetitive blockade of α and β adrenoreceptors; ; - an increase in refractory periods and a decrease in the excitability of the atrial and ventricular myocardium, as well as an increase in the refractory period of the AV node; - a slowdown in the duration and an increase in the duration of the refractory period in Additional effects of the AV conduction. Other effects: - lack of negative inotropic action by ingestion; - decrease in oxygen consumption by the myocardium due to a moderate decrease in OPSS and heart rate; - increase in coronary blood flow due to direct effects on the smooth muscles of the coronary arteries; - maintenance of cardiac output during by reducing the pressure in the aorta and reducing OPSS; —the effect on thyroid hormone metabolism: inhibiting 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 the drug has been taken internally, 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 within 10–30 days after its withdrawal should be taken into account.
Pharmacokinetics
Absorption The bioavailability after oral administration in different patients ranges from 30% to 80% (average value of about 50%). After a single dose of amiodarone inside Cmax in the blood plasma is reached in 3-7 hours. However, the therapeutic effect usually develops a week after the start of the drug (from several days to 2 weeks). Distribution Binding to plasma proteins is 95% (62% with albumin , 33.5% - with beta-lipoproteins). Amiodarone has a large Vd. 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. Metabolism Amiodarone is metabolized in the liver using isoenzymes CYP3A4 and CYP2C8. Its main metabolite, dezethylamidarone, is pharmacologically active and may enhance the antiarrhythmic effect of the main compound. Amiodarone and its active metabolite dezethylamidarone in vitro have the ability to inhibit isoenzymes CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and dezethylamodarone also demonstrated the ability to inhibit some transporters, such as P-glycoprotein (P-gp) and a carrier of organic cations (POC2). In vivo, there was an interaction of amiodarone with the substrates of CYP3A4, CYP2C9, CYP2D6 and P-gp isoenzymes. the patient. The main route of elimination of amiodarone is the intestine. Amiodarone and its metabolites are not excreted by hemodialysis. Amiodarone has a long T1 / 2 with large individual variability (therefore, when selecting a dose, for example, increasing or decreasing it, it should be remembered that at least 1 month is necessary to stabilize the new plasma concentration of amiodarone). phases: initial T1 / 2 (first phase) - 4-21 h, T1 / 2 in the 2nd phase - 25-110 days. After prolonged ingestion, the average T1 / 2 is 40 days.After discontinuation of the drug, the complete elimination of amiodarone from the body can last for several months. Each dose of amiodarone (200 mg) contains 75 mg of iodine. Part of iodine is released from the drug and is detected in the urine as iodide (6 mg per 24 h with a daily dose of amiodarone 200 mg). Most of the iodine remaining in the composition of the drug is excreted through the intestine after passing through the liver, but with prolonged use of amiodarone, the concentration of iodine in the blood can reach 60-80% of the concentrations of amiodarone in the blood. The use of loading doses, which is aimed at rapid accumulation of amiodarone in the tissues, in which its therapeutic effect is manifested. Pharmacokinetics in special clinical cases. Due to the insignificance of the drug excretion by the kidneys in patients with renal failure do not require dose adjustment of amiodarone.
Indications
Prevention of life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be started in the hospital with careful cardiomonitoring). recurrent sustained supraventricular paroxysmal tachycardia in patients without organic disease Evania of the heart when other classes of antiarrhythmic drugs are not effective or there are contraindications to their use; - documented bouts of recurrent, stable supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome. in high-risk patients, patients after a recent myocardial infarction who have more than 10 ventricular extrasystoles in 1 h, clinical manifestations of chronic heart failure and a reduced left ventricular ejection fraction (less than 40%). Cordarone can be used in the treatment of rhythm disorders in patients with coronary artery disease and / or left ventricular function disorders.
Contraindications
SSS (sinus bradycardia, sinoatrial block), except when corrected by an artificial pacemaker (danger of a sinus node stopping) - AV II and III degree blockade in the absence of an artificial pacemaker (pacemaker); - hypokalemia, hypomagnemia, - interstitial lung disease - thyroid dysfunction (hypothyroidism, hyperthyroidism); - congenital or acquired lengthening of the QT interval; - combination with drugs that can lengthen the QT interval and cause the development of paroxysmal tachycardias, including cholera tachycardia eyeglass type pirouette (torsade de pointes): antiarrhythmic drugs of class I A (quinidine, gidrohinidin, disopyramide, procainamide); class III 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, Tiapride, veralipride), butyrophenones (duroperidol, galopal, galopolydone) 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; - age up to 18 years (efficacy and safety have not been established); - pregnancy; - lactation period; - lactose intolerance (lactase deficiency), glucose-galactose malabsorption syndrome (the preparation contains lactose); - hypersensitivity to iodine, amiodarone or auxiliary substances of the drug.
Precautionary measures
Do not exceed the recommended dose. With caution, it should be used for decompensated or severe chronic (III-IV functional class according to the NYHA classification) cardiac failure, liver failure, bronchial asthma, severe respiratory failure, in elderly patients (high risk of severe bradycardia), with AV blockade I degree.
Use during pregnancy and lactation
Pregnancy The 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. Because the fetus begins to bind iodine only from the 14th week of pregnancy (amenorrhea),No effect of amiodarone is expected in case of its earlier use. Excess iodine when using the drug after this period can lead to 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, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit exceeds risks (with life-threatening ventricular arrhythmias). The lactation period of amiodarone is excreted in breast milk in significant quantities, so it is against cauldron during lactation (during this period the drug should be discontinued or stop breastfeeding).
Dosage and administration
The drug should be taken only as prescribed by a doctor. Cordarone pills are taken orally before meals and washed down with a sufficient amount of water. Loading (saturating) dose: different saturation schemes can be applied.
Side effects
Since the cardiovascular system: often - bradycardia, usually moderate, the severity of which depends on the dose of the drug; infrequently - 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); Based on the available data, it is impossible to determine whether the occurrence of these rhythm disturbances is caused by the action of Cordarone, the severity of cardiovascular disease, or is a consequence of treatment failure. These effects are observed mainly in cases of the use of the drug Cordarone together with drugs that prolong the period of ventricular repolarization of the heart (QTc interval) or in case of electrolyte disturbances in the blood. Very rarely - marked bradycardia or, in exceptional cases, the sinus node arrest, which were noted in some patients (patients with sinus dysfunction and elderly patients), vasculitis; the frequency is unknown - the progression of chronic heart failure (with prolonged use), ventricular tachycardia such as pirouette. On the part of the digestive system: very often - nausea, vomiting,dysgeusia (dulling or loss of taste), usually occurring when the loading dose is applied and passing after it is reduced. From the side of the liver and biliary tract: very often - an isolated increase in serum transaminase activity, usually moderate (1.5–3 times 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 over 6 months, chronic liver damage should be suspected. On the part of the respiratory system: often - pulmonary toxicity, sometimes fatal (alveolar / interstitial pneumonitis or fibrosis, pleurisy, bronchiolitis obliterans with pneumonia ). Although these changes may lead to the development of pulmonary fibrosis, they are mainly reversible with the early cancellation of amiodarone and with or without the use of GCS. Clinical manifestations usually disappear within 3-4 weeks. Restoration of the X-ray picture and lung function occurs more slowly (several months). The occurrence of a patient taking amiodarone, severe dyspnea or dry cough, both accompanied and not accompanied by deterioration of the general condition (increased fatigue, weight loss, increased body temperature) requires a chest X-ray and, if necessary, discontinuation of the drug. Very rare - bronchospasm (in patients with severe respiratory failure, especially in patients with bronchial asthma), acute respiratory distress syndrome (sometimes fatal and sometimes directly after surgical interventions; the possibility of interaction with a high concentration of oxygen is assumed.) Unknown frequency - pulmonary hemorrhage. On the part of the organ of vision: very often micro-deposits in the corneal epithelium consisting of complex lipids, including lipofuscin, are usually limited to the pupil area and do not require stopping treatment and disappear after drug withdrawal,sometimes they can cause visual impairment in the form of a colored halo or blurred outlines in bright light; very rarely - optic neuritis / optic neuropathy (connection with amiodarone has not yet been established; however, since optic neuritis can lead to blindness, when blurred vision or visual acuity appears while taking Cordarone, a full ophthalmological examination is recommended, including endoscopy, and in case of detection of optic neuritis, stop taking the drug). On the part of the endocrine system: often - hypothyroidism (weight gain, chilliness, apathy, decreased Naya activity, somnolence, excessive compared to the expected effect of amiodarone, bradycardia). The diagnosis is confirmed by the detection of elevated serum TSH levels (using a hypersensitive TSH assay); normalization of thyroid function is usually observed within 1-3 months after discontinuation of treatment; in situations involving a danger to life, treatment with amiodarone can be continued with the simultaneous additional prescription of L-thyroxine under the control of serum TSH levels. There is also often hyperthyroidism, sometimes fatal, which can occur during and after treatment ( hyperthyroidism that developed several months after the abolition of amiodarone). Hyperthyroidism proceeds more covertly with a small number of symptoms: a slight unexplained loss of body weight, a decrease in antiarrhythmic and / or antianginal efficacy; Mental disorders in elderly patients or even thyrotoxicosis. The diagnosis is confirmed by the identification of a reduced serum TSH level (using a hypersensitive TSH assay). If hyperthyroidism is detected, amiodarone should be canceled. Normalization of thyroid function usually occurs within a few months after discontinuation of the drug. At the same time, clinical symptoms normalize earlier (in 3-4 weeks), than normalization of the level of thyroid hormones occurs. Severe cases can be fatal, so in such cases urgent medical intervention is required. Treatment in each 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 delivery, it is recommended to start treatment immediately: use of antithyroid drugs (which may not always be effective in this case), treatment of GCS ( 1 mg / kg), which lasts a long time (3 months), beta-blockers. Very rarely - a violation of the secretion of ADH. On the side of the skin and subcutaneous tissues: very often - photosensitization; often (in case of prolonged use of the drug in high daily doses) - grayish or bluish pigmentation of the skin (after cessation of treatment, this pigmentation slowly disappears); very rarely - erythema (during radiation therapy), skin rash (usually not very specific), alopecia, exfoliative dermatitis, alopecia; frequency is unknown - urticaria. For the nervous system: often - tremor or other extrapyramidal symptoms, sleep disturbances, nightmares; infrequently - 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 (brain pseudotumor), headache. From the genitals and breast: very rarely - epididymitis, impotence. From the hematopoietic system: very rarely - thrombocytopenia, hemolytic anemia, aplastic anemia. reactions: frequency is unknown - angioedema (angioedema). Laboratory and instrumental data: very rarely - an increase in serum creatinine concentration. General disorders: frequency is unknown TSNA - granuloma formation, including bone marrow granulomas.
Overdose
Symptoms: when ingesting very large doses, several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal ventricular tachycardia such as pirouette and liver damage are described. Slowing down of AV conduction, strengthening of already existing heart failure is possible. Treatment: gastric lavage, use of activated carbon if the drug is taken recently, in other cases symptomatic therapy is carried out: for bradycardia, beta-adrenostimulants or pacemaker, for ventricular tachycardia such as pirouette, / in the introduction of magnesium salts or cardiac stimulation. Neither amiodarone nor its metabolites are removed during hemodialysis. There is no specific antidote.
Interaction with other drugs
Drugs that can cause bidirectional ventricular tachycardia such as pirouette or increase the duration of the QT interval. Drugs that can cause ventricular tachycardia such as pirouette. Combined therapy with drugs that can cause ventricular tachycardia like pirouette is contraindicated because the risk of developing potentially lethal ventricular tachycardia of the pirouette type 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, flufenazine), benzamides (amisulpride, sultoprid, sulprid, Tiapride, veralliprid), butyrophenones (droperidol, I used (I), (iberopropyl), butyrophenones (Iberopropylamine) 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. Drugs capable of increasing the QT interval, combined administration of amiodarone with drugs capable of increasing the QT interval should be based on a careful assessment of the expected benefit and potential risk for each patient (the possibility of increasing the risk of ventricular torsion of the type of pirouette) when using these combinations is necessary constantly monitor patients' ECG (to detect prolongation of the QT interval), the content of potassium and magnesium in the blood. Patients use of fluoroquinolones, including moxifloxacin, should be avoided. Preparations that slow heart rate or cause automatism or conduction disorders Combined therapy with these drugs is not recommended. Beta-blockers, slow calcium channel blockers, which reduce heart rate (verapamil, diltiazem) may cause blotters. (development of excessive bradycardia) and conductivity. Drugs capable of inducing hypokalemia. Not recommended combinations with laxatives that stimulate peris. altiku intestine that can cause hypokalemia, which increases the risk of ventricular tachycardia type pirouette.When combined with amiodarone, other groups of laxatives should be used. Combinations that require caution when used with diuretics that cause hypokalemia (in monotherapy or in combination with other drugs); - with systemic corticosteroids (glucocorticoid, mineralocorticoid), tetrakozaktidom; in / in the introduction). It is necessary to prevent the development of hypoglycemia, and in case of its occurrence to restore to normal levels of potassium in the blood, to control the concentration of electrolytes in the blood and EC G (for possible prolongation of the QT interval), and in the event of ventricular tachycardia such as pirouette, antiarrhythmic drugs should not be used (ventricular cardiac stimulation should be initiated; possibly in the introduction of magnesium salts). Preparations for inhalation anesthesia The possibility of the following serious complications was reported patients taking amiodarone during general anesthesia: bradycardia (resistant to the administration of atropine), reduction of blood pressure, conduction disturbances, reduction of cardiac output. There are very rare cases of severe complications of the respiratory system, sometimes fatal (acute respiratory distress syndrome of adults, which developed immediately after surgery, and the occurrence of which is associated with high concentrations of oxygen). Preparations that slow the heart rate (clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, takrin, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpineDisk of developing excessive bradycardia (cumulative effects) projects) .Vliyanie amiodarone preparatyAmiodaron other drugs and / or its metabolite dezetilamiodaron inhibit isozymes CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein may increase the systemic exposure of drugs which are their substrates. In connection with the prolonged T1 / 2 of amiodarone, this interaction can be observed even several months after the cessation of its administration. Medications that are substrates for P-gp Amiodarone is an inhibitor of P-gp. It is expected that its joint intake with drugs that are substrates of P-gp will lead to an increase in the systemic exposure of the latter. Cardiac glycosides (digitalis preparations) The possibility of the occurrence 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 control possible clinical and electrocardiographic manifestations of digitalis intoxication. Reduction in digoxin dosage may be required. Dabigatran. Care must be taken with simultaneous use of amiodarone with dabigatran because of the risk of bleeding. It may be necessary to adjust the dose of dabigatran in accordance with the instructions in its instructions for use. Medications that are substrates of CYP2C9 isoenzyme Amiodarone increases the concentration of drugs that are substrates of CYP2C9 isoenzyme, such as warfarin or phenytoin, by inhibiting cytochrome P450 2С. may increase the effects of indirect anticoagulant, which increases the risk of bleeding. Prothrombin time should be monitored more often (by determining the MHO) and the anticoagulant doses should be adjusted both during treatment with amiodarone and after discontinuation of it. Phenytoin When phenytoin is combined 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 are necessary at the first signs of overdose. It is desirable to determine the concentration of phenytoin in the blood plasma. Medicinal preparations that are CYP2D6 isoenzyme substrates which are substrates of CYP3A4 isoenzyme with a combination of amiodarone, an inhibitor of the isoenzyme CYP3A4, with these drugs about increasing their plasma concentrations, which can lead to increased toxicity and / or enhance the pharmacodynamic effects and may require a reduction of their doses. These drugs are listed below. Cyclosporin A combination of cyclosporine with amiodarone may increase plasma concentrations of cyclosporine,dose adjustment is necessary. FentanylCombination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of its toxic effects. HMG-CoA reductase inhibitors (statins) (simvastatin, atorvastatin and lovastatin) Increase the risk of muscular toxicity of statins when they are used concurrently with amiodarone. The use of statins that are not metabolized by the CYP3A4 isoenzyme is recommended. Other drugs that are metabolized by the CYP3A4 isoenzyme are: lidocaine (the risk of developing sinus bradycardia and neurological symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (risk of increasing its side effects) (midazolam) psychomotor effects), triazolam, dihydroergotamine, ergotamine, colchicine. The drug, which is a substrate of CYP2D6 and CYP3A4 isoenzymes - dextromethorphanAmiodarone inhibits CYP2D6 and CYP3A4 isoenzymes and can theoretically increase the plasma concentration of dextromethorphan. KlopidogrelKlopidogrel is an inactive thienopyrimidine drug, 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. The effects of other drugs on amiodarone CYP3A4 and CYP2C8 isoenzyme inhibitors can have the potential to inhibit the metabolism of amiodarone and increase its blood concentration and, accordingly, its pharmacodynamic and side effects. CYP3A4 inhibitors (for example, grapefruit juice and some drugs, such as cimetidine, and HIV protease inhibitors (including during treatment with amiodarone is a potent inducer of CYP3A4 isoenzyme. In this regard, it is theoretically possible to decrease the plasma concentration of amiodarone and decrease its effect (there are no clinical data).
special instructions
Since The side effects of amiodarone are dose-dependent, patients should be treated with minimal effective doses to minimize the possibility of their occurrence. Patients should be warned to avoid direct sunlight or take protective measures during treatment (for example, using sunscreen, wearing appropriate clothing). ) .Monitoring of treatment. Before starting receiving amiodarone, it is recommended to conduct an ECG study and determine the content 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) and transaminase activity and other indicators of liver function. In addition, due to the fact that amiodarone may cause hypothyroidism or hyperthyroidism, especially in patients with thyroid disease in history, it should be given conduct clinical and laboratory (serum TSH concentration, determined using ultra-sensitive analysis of TSH) screening for the identification of functional disorders and diseases of the thyroid gland. During treatment with amiodarone and for several months after it is discontinued, the patient should be regularly examined for 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 concentration (using an ultrasensitive assay for TSH). Patients receiving long-term treatment for rhythm disturbances have reported cases of increased ventricular defibrillation and / or increased pacemaker stimulation or implanted defibrillator, which may reduce the effectiveness of these devices. Therefore, before starting or during treatment with amiodarone, they should be regularly checked for proper functioning. Regardless of the presence or absence of pulmonary symptoms during amiodarone, it is recommended that x-ray examination of the lungs and pulmonary functional tests be performed every 6 months. The appearance of shortness of breath or dry cough, both isolated and accompanied by deterioration of the general condition (fatigue, weight loss,fever), may indicate pulmonary toxicity, such as interstitial pneumonitis, suspicion of the development of which requires an x-ray examination of the lungs and pulmonary functional tests. Due to the lengthening period of ventricular repolarization, the pharmacological effect of Cordaron causes certain ECG changes: lengthening the QT interval, QTc (corrected), the appearance of U waves is possible. An increase in the QTc interval of no more than 450 ms or no more than 25% of the initial magnitude is acceptable. s. 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 the drug Cordarone. When AV block II and III are developed, sinoatrial block or two-bundle intraventricular block, treatment should be stopped. In the event of an I-degree AV blockade, observation should be strengthened.