Cordarone tablets 200mg
A description of the dosage form
Tablets: round divisible tablets white or white with kremovatym color engraved on one side - a symbol of a heart, and "200". The tablets can be easily separated along a fault line under normal conditions of use.
Solution: clear solution pale yellow.
Before and during treatment is recommended ECG study. Lengthening of the period due to ventricular repolarization of the heart, the pharmacological effect of Cordarone causes certain changes ECG interval prolongation QT, QTc (corrected), the appearance of waves U. Permissible increase in the QTc interval to 450 ms or 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 possible actions proaritmogennogo Cordarone.
Older people may slow heart rate with the development of bradycardia.
The appearance of dyspnea or nonproductive cough may be due to toxic effects on the lungs Cordarone (see "Side Effects").
With the development of AV block II-III degree, sinoatrial block or intraventricular block two-beam treatment should be discontinued.
Since Cordarone contains iodine, before and during treatment is recommended to study the function of the thyroid gland. Cordaron can skew the results of radionuclide studies of thyroid cancer, but does not affect the accuracy of the determination of T3, T4 and TSH in blood plasma.
Before and during treatment is recommended to determine the level of potassium in the blood serum.
Intravenous administration of Cordarone should normally be used in the form in / infusion, and not as an injection syringe because of the risk of hemodynamic disturbances (hypotension, acute cardiovascular insufficiency).
Intravenous administration of Cordarone syringe by injection should be performed only in emergency situations when no other therapeutic options, and only of coronary care units with continuous electrocardiographic monitoring.
With the introduction of Cordarone syringe by injection dose of about 5 mg / kg should be administered for at least 3 minutes. Injections should not be repeated in less than 15 minutes after the first injection, even if the latter consisted only of one vial (possible irreversible collapse).
Do not mix in the same syringe with other drugs. If necessary, long-term treatment should go to / v infusion (see "Dosage and Administration").
Cordarone for in / injection should be used only in specialized hospital wards constantly monitored (ECG, blood pressure).
Use with caution in the case of hypotension, severe respiratory failure, with decompensated cardiomyopathy or severe heart failure.
General anesthesia: an anesthesiologist before surgery should be made aware that the patient is taking amiodarone (see "Interactions").
Before starting treatment with Cordarone is recommended that ECG, the level of thyroid hormone (T3, T4 and TSH), and serum potassium.
Side effects of the drug (see "Side Effects") is usually dependent on the dose, so be careful when determining the lowest effective maintenance dose to avoid or minimize the occurrence of unwanted effects.
Patients should be warned that they are in the course of treatment to avoid sunlight or take protective measures (such as sunscreen).
Amiodarone can cause thyroid cancer, especially in patients with impaired thyroid function in an individual or family history. Therefore, before starting treatment, during treatment and several months after completion of treatment should conduct a careful clinical and laboratory monitoring. If you suspect a thyroid dysfunction should be the measurement of TSH in serum.
Structure and Composition
Divisible tablets 1 tablet.
Amiodarone hydrochloride 200 mg
excipients (1 tablet weighing 350 mg): lactose monohydrate 200 mesh. - 71 mg corn starch - 66 mg Valium K90F - 6 mg colloidal anhydrous silica - 2.4 mg of magnesium stearate - 4.6 mg
in blister 10 pcs., in box 3 blisters.
Solution for intravenous injection of 3 ml
Amiodarone hydrochloride 150 mg
Excipients (per vial): benzyl alcohol - 60 mg polysorbate 80 - 30 mg, and water for injection - 3 ml, nitrogen - qs
in vials of 3 ml in a box 6 pcs.
After oral administrationabsorbed slowly (30-50%), the rate of absorption is subject to significant fluctuations. It has a wide distribution range.
Most amiodarone accumulates in adipose tissue, liver, lungs, spleen, and cornea.
Bioavailability after oral administration ranges from 30 to 80% in different patients (mean 50%). After a single dose Cmax in plasma is reached after 3-7 hours therapeutic effect usually occurs within 1 week after the start of treatment (from a few days to two weeks.)
Has a long half-life and large scale individual variability (20-100 days). During the first days of treatment, the drug accumulates in almost all tissues, especially in the adipose tissue. Excretion begins in a few days and sustained plasma concentrations are reached within one to several months, depending on the individual patient.
Based on these characteristics, it is necessary to use the initial (loading) dose for rapid accumulation of the drug in tissues, which is necessary to achieve a therapeutic effect.
Metabolized in the liver. The main metabolite - dezetilamiodaron - pharmacologically active and may increase the antiarrhythmic effect of a basic compound. Each dose of Cordarone (200 mg) contains 75 mg of iodine, and it was determined that 6 mg of which is released in the form of free iodine. In long-term treatment of its concentration can reach 60-80% of the concentrations of amiodarone. Given the ability to accumulation and the associated greater variability of pharmacokinetic parameters, half-life data are contradictory. Excretion ingestion occurs in two phases: the first period - 4-21 hours, in the second phase T1 / 2 - 25-110 days. After a lengthy oral average T1 / 2 - 40 days (this is important when choosing the dose, as needed, at least 1 month to stabilize the plasma concentration and elimination from the body can take more than 4 months). After complete removal of the drug from the body continues for several months. Should take into account the presence of pharmacodynamic action Cordarone for 10 days and up to 1 month after its cancellation.
Appears mainly in the bile and feces.
Slight excretion of the drug in the urine can assign the usual doses in patients with renal insufficiency. Relationship to plasma proteins - 95% (62% - with albumin, 33.5% - with beta-lipoproteins).
Amiodarone and its metabolites undergo dialysis.
At / in the introduction Cordarone its activity reaches a maximum after 15 minutes and disappears in about 4 hours after administration. Despite the fact that the number entered Cordarone levels decline rapidly, reaching saturation tissue preparation. In the absence of repeated injections of the drug gradually appear. the resumption of administration or appointment of the drug orally formed his cloth stock.
Antiarrhythmic properties: Extend the third phase of the action potential of cardiomyocytes, mainly by blocking potassium currents (III class classification Vaughan Williams); decreases automaticity of sinus node, reducing the frequency of heart rate, not competitively blocks the alpha-and beta-adrenergic receptors in the heart, slowing velocity of conduction in the sinoatrial area in the atria and AV connections, which is more pronounced for frequent heart rhythm, no effect on intraventricular conduction, increases the refractory periods of atrial, ventricular and AV connections, while reducing the excitability of atrial and ventricular slows conduction of excitation additional atrioventricular connections and extend their refractory periods.
Anti-ischemic properties: moderately reduces peripheral resistance and heart rate, leading to a reduction in myocardial oxygen demand, causing the blockade of alpha-and beta-adrenergic receptors in the heart is not the competitive type, increases coronary blood flow by a direct effect on the smooth muscle of myocardial arteries supports cardiac output by reducing the pressure in the aorta and peripheral resistance.
Other effects: decreases myocardial contractility, mainly after / in the introduction by the beta-blocking effect, affects the exchange of thyroid hormones, inhibits the conversion of T3 to T4 (thyroxine-blockade deyodinazy 5) and blocks the capture of these hormones cardiocytes and hepatocytes, which leads to a weakening of the stimulating effect of thyroid hormones on the myocardium, determined in plasma for 9 months after cessation of administration.
Cupping paroxysmal tachycardia:
- Ventricular paroxysmal tachycardia;
- Supraventricular paroxysmal tachycardia with high frequency of contractions of the ventricles, especially in the face WPW-syndrome.
And sustained relief of paroxysmal atrial fibrillation (AF) and atrial flutter.
- Life-threatening ventricular arrhythmias and ventricular fibrillation of the heart (treatment should be initiated in hospital with careful kardimonitornom control);
- Supraventricular paroxysmal tachycardia (documented recurrent episodes of paroxysmal supraventricular tachycardia resistant patients with organic heart disease, documented episodes of recurrent sustained supraventricular paroxysmal tachycardia in patients without organic heart disease when other classes of anti-arrhythmic drugs are ineffective or have contraindications to their use, documented episodes of recurrent sustained supraventricular paroxysmal tachycardia in patients with WPW-syndrome);
- Atrial fibrillation (AF) and atrial flutter.
Prevention of sudden arrhythmic death in high-risk patients with recent myocardial infarction, with more than 10 ventricular premature beats in 1 h, the clinical manifestations of chronic heart failure and reduced left ventricular ejection fraction (<40%).
Cordarone is particularly recommended for patients with organic heart disease (including CHD), followed by left ventricular dysfunction.
Cordarone injection form is intended for use in the hospital, in cases when a rapid achievement of the antiarrhythmic effect, or if it can not be taken orally.
Tablets: hypersensitivity to iodine and / or amiodarone, sick sinus syndrome (sinus bradycardia, sinoatrial block), unless the correction of an artificial pacemaker (risk of "stopping" the sinus node) violations AV and intraventricular conduction (AV block II-III degree, bundle-branch block, block) in the absence of an artificial pacemaker (pacemaker), a combination of a drug that can cause polymorphic ventricular tachycardia of the "pirouette", thyroid dysfunction (hypothyroidism, hyperthyroidism), hypokalemia, cardiac failure (decompensated), pregnancy , lactation (see "Pregnancy and lactation"), age 18 years (the efficacy and safety have not been established), co-administration of MAO inhibitors, interstitial lung disease.
Injections: hypersensitivity to iodine and / or amiodarone, sick sinus syndrome (sinus bradycardia, sinoatrial block), unless the correction of an artificial pacemaker (risk of "stopping" the sinus node); AV block II-III degree, intraventricular conductivity (two and trehpuchkovye block) in the absence of an artificial pacemaker (pacemaker) - in these cases, amiodarone / O can be used in specialized departments under the guise of an artificial pacemaker (pacemaker), acute cardiovascular collapse (shock, collapse); marked hypotension, a combination of a drug that can cause polymorphic ventricular tachycardia of the "pirouette» (torsade de pointes) (see "Interactions"), thyroid dysfunction (hypothyroidism, hyperthyroidism), pregnancy, lactation (see "Pregnancy and breast-feeding "), age 18 years (the efficacy and safety have not been established).
Intravenous injection is contraindicated in case of serious violations of the lungs (interstitial lung disease), cardiomyopathy or decompensated heart failure (possibly degradation).
Be wary of chronic heart failure, liver failure, asthma, in old age (high risk of severe bradycardia).
Dosage and administration
Tablets. Inside. Loading dose - in the hospital - the initial dose, divided into several stages, ranging from 600-800 mg / day to a maximum of 1200 mg / day to a total dose of 10 g (usually within 5-8 days) out - the initial dose, divided into several stages, ranging from 600 to 800 mg / day to a total dose of 10 g (usually within 10-14 days).
Maintenance dose - 3 mg / kg / day and can range from 100 to 400 mg / day with a single dose. Should use the lowest effective dose according to individual therapeutic outcome.
Since Cordarone has a very long half-life, it can be taken every other day (200 mg may be given every other day, and it is recommended to take 100 mg daily), or you can take a break (2 days per week).
Injection. In / in, in / injection.
In / in: loading dose - the initial dose is 5-7 mg / kg in 250 mL of 5% dextrose (glucose) for 30-60 minutes, the therapeutic effect occurs within the first minutes of administration, and gradually disappears, requiring speed correction administration according to the results of treatment, supportive care - constant or intermittent (2-3 times a day) in / infusion in 5% dextrose (glucose) for several days at a dose of 1200 mg / day to a total dose '10 After the on / in a loading dose instead of continuing in / infusion possible cordaron into tablets at a dose of 600-800 up to 1200 mg / day to a total dose '10 From the first day on / in the appropriate to begin a gradual transition to oral medication.
In / injection (see "Special Instructions"): a dose - 5 mg / kg - is introduced in any case for at least 3 minutes. Do not dial in one syringe with other drugs.
Instructions for use: from the pharmaceutical properties of the drug should not be used concentrations below 600 mg / l. For solution for on / in the only use 5% dextrose (glucose).
Pregnancy and breast feeding
Since the drug acts on the thyroid gland of the fetus, amiodarone is contraindicated in pregnancy except in special cases (life-threatening ventricular arrhythmias). Amiodarone is allocated in breast milk in significant amounts, so it is contraindicated in nursing mothers. During feeding the drug should be discontinued.
Combined use is contraindicated with drugs that can cause polymorphic ventricular tachycardia paroxysmal type "pirouette» (torsade de pointes) (see "Contraindications"):
- Antiarrhythmic drugs, including drugs of class IA, bepridil, sotalol;
- Drugs that do not possess antiarrhythmic activity, including vincamine, sultoprid, erythromycin, (w / w), pentamidine in the case of parenteral administration, because there is the risk of paroxysmal tachycardia with the possibility of death.
Not recommended for combination therapy with the following drugs:
- Beta-blockers and some CCBs (verapamil, diltiazem), as possible violation of automatism (bradycardia) and conduction;
- Laxatives that promote bowel movements, as they can cause hypokalemia, and thus increase the risk of paroxysmal tachycardia, should appoint a different type of laxative.
Caution should be used in combination with Cordarone following drugs:
- Means that cause hypokalemia, including diuretics (alone or in combination with other drugs), corticosteroids (glucocorticoids, mineralocorticoids) tetrakozaktid, amphotericin B /
Cardio-vascular system: bradycardia, which basically is a moderate and dose-dependent. In some cases (sinus node dysfunction, elderly patients) are described bradycardia or (in exceptional cases) sinus cardiac arrest. Rare are conduction disturbances (sinoatrial block, AV block of various degrees, intraventricular block). There are reports of the emergence of new arrhythmias or worsening of existing ones, in some cases - followed by cardiac arrest. From the information available it is impossible to determine the reason for this use of the drug or is associated with the severity of heart disease, or it may be due to treatment failure. These effects are observed mainly in cases of Cordarone with drugs that prolong cardiac ventricular repolarization period (interval QTc) or electrolyte imbalance (see "Interactions").
For part of the view: mikrodepozity in cornea, is almost always present, is usually limited to the pupil. Sometimes they can cause abnormalities in the appearance of the colored halo in bright light or a feeling of fog. Mikrodepozity the cornea consists of a complex of lipids and reversible upon discontinuation of the drug.
Described several cases of neuropathy / optic neuritis, the relationship with amiodarone are not currently installed. However, since visual neuropathy can lead to blindness, when a blurred vision or decrease in visual acuity in patients receiving Cordarone recommended for a full eye examination, including fundoskopiyu. Cases of visual neuropathy and / or optic neuritis require a decision on the feasibility of using Cordarone.
For the skin: photosensitivity - patients should be warned that they are in the course of treatment to avoid sunlight (or UV rays). There may also be cases of erythema during radiotherapy.
There have been reports of skin rashes, usually non-specific, including individual cases of exfoliative dermatitis; relationship with the drug is not formally established.
Prolonged use of the drug in high daily doses may be a grayish or bluish pigmentation of the skin after treatment, this pigmentation is slowly disappearing.
From a metabolism: in connection with the chemical structure of amiodarone may appear in some biochemical parameters reflecting the function of the thyroid gland - increased serum T3, T4 and the level remains normal or slightly reduced. In such cases, in the absence of clinical signs of thyroid dysfunction, the drug is required.
Hypothyroidism. On the development of hypothyroidism may suggest the following clinical symptoms, usually mild: weight gain, reduced activity, excessive compared to the expected effect of amiodarone bradycardia. The diagnosis is confirmed a distinct increase in serum TSH levels. Normalization of thyroid function usually occurs within 1-3 months after treatment cessation. In situations of danger to life, treatment with amiodarone may be continued with simultaneous supplementation of levothyroxine. Serum TSH level is a guide to the dose of levothyroxine.
Hyperthyroidism may occur during and after treatment for several months. The diagnosis of hyperthyroidism may indicate the following clinical symptoms are usually mild: weight loss, arrhythmia, angina, heart failure. The diagnosis is confirmed by a clear decrease in serum TSH levels. Amiodarone should be repealed. Normalization of thyroid function usually occurs within a few months after drug withdrawal. At the same clinical symptoms normalized before the normalization of hormone levels, which reflect the function of the thyroid gland. In severe cases, sometimes fatal, requires urgent medical intervention. Treatment in each case is individually (antithyroid drugs (which may not always be effective), corticosteroid therapy, beta-blockers).
Of the liver: early treatment can separate cases transaminase elevations in serum, which is usually moderate (1.5-3 times higher than normal), elevated transaminases, decreased with decreasing the dose or even spontaneously.
Described several cases of severe liver dysfunction with elevated liver enzymes in the serum and / or jaundice (among which were fatal), and in such cases, treatment should be discontinued.
There are also reports of chronic diseases of the liver (steatosis, cirrhosis). Clinical symptoms and changes in laboratory parameters may be minimal (possible hepatomegaly, hepatic transaminase levels increased to 1.5-5 times compared with normal), so in the course of treatment recommended regular monitoring of liver function.
The respiratory system: There are cases (pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans with pneumonia), sometimes resulting in death.
In patients with progressive exertional dyspnea, regardless of the deterioration of their general condition (increased fatigue, weight loss, fever), before starting therapy should be chest x-ray.
These disorders are mostly reversible with early cancellation of amiodarone. Clinical symptoms usually resolve within 3-4 weeks, and then there is a slow recovery of radiographic and lung function (several months). Therefore, you should consider re-evaluation of treatment with amiodarone and the possibility of corticosteroid therapy.
Described several cases of bronchospasm in patients with severe respiratory disorders, especially in patients with bronchial asthma.
Several cases of acute respiratory distress syndrome, adult, sometimes resulting in fatal, usually after surgery.
Nervous system disorders: Rare sensorimotor peripheral neuropathy and / or myopathy, usually reversible after discontinuation of the drug; extrapyramidal tremor, cerebellar ataxia, in rare cases - benign intracranial hypertension (pseudotumor of the brain), nightmares.
Others: digestive disorders (nausea, vomiting, taste disturbances), commonly found in the application of the initial dose and reduced at lower doses, alopecia. Described several cases of epididymitis, and a few cases of impotence, relationship with the treatment has not been established. Know a few rare cases with different clinical manifestations that suggest a hypersensitivity reaction: vasculitis, renal involvement with an increase in serum creatinine, and thrombocytopenia. Also describes a few exceptional cases of hemolytic or aplastic anemia.
Local reactions: phlebitis, which can be avoided with the use of a central venous catheter.
Systemic reactions: hot flashes, sweating, lowering blood pressure, usually mild and transient (cases of severe hypotension or collapse have been reported with overdose or too rapid an injection), moderate bradycardia (in some cases, especially in elderly patients, bradycardia and Exceptionally stop sinus, requiring discontinuation of treatment). There are cases of worsening of arrhythmia, sometimes accompanied by heart failure. From the information available it is impossible to determine the reason for this use of the drug or is associated with the severity of heart disease, or it may be due to treatment failure. These effects are observed mainly in cases of Cordarone with drugs that prolong cardiac ventricular repolarization period (interval QTc) or electrolyte imbalance (see "Interactions").
Elevated liver enzymes in the blood serum, which is usually moderate (1.5-3 times higher than normal), described at the beginning of treatment, they typically normalized dose reduction or even spontaneously.
There are reports of several cases of acute liver failure with high liver enzymes in the blood and / or jaundice, among which there were and deadly. With a significant increase in transaminases, treatment should be discontinued. In the treatment of Cordarone recommended periodic monitoring of liver function.
In a few rare cases and after i / v injection anaphylactic shock, have been observed, benign intracranial hypertension (pseudotumor of the brain), bronchospasm and / or apnea in patients with severe respiratory failure, especially in patients with bronchial asthma.