Amiodarone-SZ - instructions for use, dose, side effects, contraindications

auxiliary substances: lactose monohydrate (milk sugar) - 70.0 mg, potato starch - 60.0 mg, calcium stearate - 4.0 mg, talc - 6.0 mg, povidone (polyvinylpyrrolidone medium molecular weight) - 10.0 mg, cellulose microcrystalline - 50.0 mg.

Description:

Tablets are white or white with a creamy shade of color, round, flat-cylindrical with a facet and a risk.

Pharmacotherapeutic group:antiarrhythmic drug

ATX: & nbsp

C.01.B.D.01 Amiodarone

Pharmacodynamics:

Antiarrhythmic drug of the III class (inhibitor of repolarization). It also has antianginal, coronarodilating, alpha and beta-adrenergic blocking, thyroid-stimulating and hypotensive actions.

Antiarrhythmic effect is due to the effect on the electrophysiological processes of the myocardium; lengthens the cardiomyocyte action potential; increases the effective refractory period of the atria, ventricles, atrioventricular (AV) node, a bundle of His and Purkinje fibers, additional ways of conducting excitation.

By blocking the "fast" sodium channels, it has effects characteristic of class I antiarrhythmics. It inhibits the slow (diastolic) depolarization of the membrane of the cells of the sinus node, causing bradycardia, depresses AV conduction (effect of antiarrhythmics IV class).

The antianginal effect is due to coronary dilatory and antiadrenergic action, a decrease in myocardial oxygen demand.Has a retarding effect on alpha and beta-adrenergic receptors of the cardiovascular system (without complete blockade). Reduces sensitivity to hyperstimulation of the sympathetic nervous system, resistance of coronary vessels; increases coronary blood flow; decreases the heart rate (heart rate); increases the energy reserves of the myocardium (by increasing the content of creatine phosphate, adenosine triphosphate and glycogen).

It is similar in its structure to thyroid hormones. The iodine content is about 37% of its molecular weight. Affects the exchange of thyroid hormones, inhibits the transformation of thyroxine (T4) into triiodothyronine (T3) (blockade of thyroxine-5-deiodinase) and blocking the seizure of these hormones by cardiocytes and hepatocytes, which leads to weakening the stimulating effect of thyroid hormones on the myocardium. The onset of action (even with the use of "loading" doses) - from 2-3 days to 2-3 months, the duration of action varies from several weeks to months (determined in blood plasma for 9 months after discontinuation of its administration).

Pharmacokinetics:

Absorption is slow and variable - 30-50%, bioavailability - 30-50%. The maximum concentration in the blood plasma (Cmax) is observed after 4-7 hours. The range of therapeutic plasma concentration is -1.2.5 mg / l (but when determining the dose, one should also bear in mind the clinical picture). The volume of distribution is 60 liters, which indicates an intensive distribution in the tissue. It has high fat solubility, is in high concentrations in adipose tissue and organs with good blood supply (concentration in adipose tissue, liver, kidneys, myocardium is higher than in plasma - respectively, 300, 200, 50 and 34 times). The pharmacokinetics of amiodarone cause the use of the drug in high loading doses. Penetrates through the blood-brain barrier (GEB) and the placenta (10-50%), is secreted with breast milk (25% of the dose received by the mother). Communication with blood plasma proteins - 95% (62% - with albumin, 33,5% - with beta-lipoproteins). Metabolised in the liver. The main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the basic compound. Perhaps also by deiodination (at a dose of 300 mg, about 9 mg of elemental iodine is released). With prolonged treatment, iodine concentrations can reach 60-80% of the concentrations of amiodarone.Given the capacity for cumulation and the large variability of pharmacokinetic parameters associated with this, the data on the half-life (T1 / 2) are inconsistent. Removal of amiodarone after oral administration is carried out in 2 phases: the initial period is 4-21 hours, in the second phase of T1 / 2 - 25-110 days. After long ingestion, the average T1 / 2 is 40 days (this is important in choosing a dose, since it may be necessary for at least 1 month to stabilize a new plasma concentration, while complete elimination may last more than 4 months). It is excreted through the intestine with bile (85-95%), the kidneys are excreted less than 1% of the dose taken internally (therefore, if there is impaired renal function, there is no need to change the dose). Amiodarone and its metabolites are not dialyzed.

Indications:

Prevention of recurrences of paroxysmal rhythm disturbances: life-threatening ventricular arrhythmias (including ventricular tachycardia, ventricular fibrillation); supraventricular arrhythmias (including with organic heart diseases, as well as ineffectiveness or impossibility of using other antiarrhythmic therapy); documented seizures of recurrentstable supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome; atrial fibrillation (atrial fibrillation) and atrial flutter.

Contraindications:

hypersensitivity to iodine, amiodarone or to other components of the drug;

syndrome of weakness of the sinus node (sinus bradycardia and sinoatrial block, in the absence of a pacemaker (risk of stopping the sinus node);

atrioventricular blockade of II-III degree, two- and three-beam blockades (with absence of a pacemaker);

severe arterial hypotension;

dysfunction of the thyroid gland (hypo- and hyperthyroidism);

pregnancy and lactation;

simultaneous reception with drugs that can lengthen the interval QT and cause the development of paroxysmal tachycardia, including polymorphic ventricular tachyarrhythmia of the "pirouette" type (torsade des pointes):

antiarrhythmic drugs of I A class (quinidine, hydroquinidine, disopyramide, procainamide); antiarrhythmic drugs of the III class (dofetilide, ibutilid, brethil tosylate); sotalol;

other (not anti-arrhythmic) drugs, such as, beprideal; wincamine;

some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine; astemizole, terfenadine; fluoroquinolones incl. moxifloxacin.

hypokalemia, hypomagnesemia;

congenital or acquired lengthening interval QT;

interstitial lung diseases;

simultaneous administration of monoamine oxidase inhibitors (MAO);

age under 18 years (effectiveness and safety not established);

lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

Carefully:

Hepatic insufficiency, bronchial asthma, old age (high risk of severe bradycardia), chronic heart failure (III-IV functional class by classification NYHA), AV blockade of the 1st degree.

Pregnancy and lactation:

A drug Amiodarone is contraindicated for use during pregnancy, because during this period the thyroid gland of the newborn begins to accumulate iodine, and the use of the drug Amiodarone in this period can provoke the development of hypothyroidism due to an increase in the concentration of iodine.

Due to the effect of the drug on the thyroid gland of the fetus, amiodarone contraindicated during pregnancy, except in special cases, when the expected benefit exceeds the risks (with life-threatening ventricular arrhythmias).

Amiodarone is excreted in breast milk in significant quantities, therefore the use of Amiodarone is contraindicated for use during lactation.

Dosing and Administration:

Tablets are taken orally before meals, with plenty of liquid.

The dosage regimen is set individually and adjusted by the doctor.

Load ("saturating") dose

In the hospital: the initial dose (divided into several doses) is 600-800 mg / day (up to a maximum dose of 1200 mg) until a total dose of 10 g is reached (usually within 5-8 days).

Out-patient: The initial dose, divided into several doses, is

600-800 mg / day until a total dose of 10 g (usually within 10-14 days).

Maintenance dose

With maintenance treatment, the lowest effective dose is applied depending on the individual reaction of the patient and is usually from 100-400 mg / day. (1-2 tablets) in 1-2 reception.

Due to the long half-life of the drug, you can take the drug every other day or take a break in taking the drug - 2 days a week.

The average therapeutic single dose is 200 mg.

The average therapeutic daily dose is 400 mg.

The maximum single dose is 400 mg.

The maximum daily dose is 1200 mg.

Side effects:

Frequency: very often (10% or more), often (1% or more, less than 10%), infrequently (0.1% or more, less than 1%), rarely (0.01% or more, less than 0.1% %), very rarely (less than 0.01%, including individual cases), the frequency is unknown (according to the available data, the frequency can not be determined).

From the cardiovascular system: often - mild bradycardia (dose-dependent); infrequently - sinoatrial blockade, AV blockade of various degrees, proaritmogenic action (strengthening of an existing arrhythmia or the emergence of a new one, including with cardiac arrest); very rarely - severe bradycardia, stopping the sinus node (in patients with sinus node dysfunction and elderly patients); frequencyis unknown - with prolonged use - the progression of symptoms of chronic heart failure.

From the digestive system: very often - nausea, vomiting, decreased appetite, a taste disorder, a feeling of heaviness in the epigastrium, an increase in the activity of "hepatic" transaminases (1.5-3 times higher than normal); often acute toxic hepatitis with an increase in the activity of "liver" transaminases and / or jaundice, including the development of hepatic insufficiency, including fatal outcome; very rarely - chronic liver failure (pseudo-alcoholic hepatitis, cirrhosis) including also fatal.

From the respiratory system: often - alveolar or interstitial pneumonitis, obliterating bronchitis with pneumonia, including fatal outcome, pleurisy, pulmonary fibrosis; very rarely - bronchospasm in patients with severe respiratory failure (especially in patients with bronchial asthma), acute respiratory syndrome, including fatal; frequency unknown - pulmonary hemorrhage.

From the sense organs: very often - the deposition of lipofuscin in the epithelium of the cornea (often subjective complaints are absent, but if the deposits are significant and partially fill the pupil,complaints about the occurrence of color halos or fuzziness of contours are possible); very rarely - optic neuritis / visual neuropathy.

From the side of metabolism: often - an increase in T4 activity under normal or a slight decrease in T3 (in the absence of clinical signs of thyroid dysfunction, treatment should not be discontinued); With prolonged application possible development of hypothyroidism, much less often - hyperthyroidism (drug cancellation is necessary); very rarely - the syndrome of ADH secretion (antidiuretic hormone).

From the skin: very often - photosensitivity; often - lead-blue or bluish skin pigmentation (with prolonged use), - after discontinuation of treatment slowly disappears within 10-14 days; very rarely - erythema (with simultaneous radiotherapy), skin rash, exfoliative dermatitis (there is no connection with taking the drug), vasculitis, alopecia.

From the central nervous system: often - tremor and other extrapyramidal disorders, sleep disturbances, including "nightmarish" dreams; rarely - peripheral neuropathy (sensory, motor, mixed) and / or myopathy; very rarely - cerebellar ataxia, benign intracranial hypertension (pseudotumour of the brain), headache.

Laboratory indicators: very rarely with prolonged use thrombocytopenia, hemolytic and aplastic anemia.

Other: very rarely - epididymitis, a decrease in potency (communication with the drug is not established), vasculitis.

Overdose:

In the case of the appearance of toxicity in the form of pro-arrhythmogenic effect, the drug is canceled. Symptoms: decrease in arterial pressure, sinus bradycardia, arrhythmias, atrioventricular blockade, aggravation of the current chronic heart failure, impaired liver function, cardiac arrest.

Treatment: gastric lavage and reception of activated charcoal, if the drug is taken recently. In other cases, symptomatic therapy is performed. There is no specific antidote, hemodialysis is not effective, amiodarone and its metabolites are not removed during dialysis. With the development of bradycardia, it is possible to use atropine, beta-adrenostimulyatorov or staging an artificial pacemaker (IWR); with tachycardia such as "pirouette" - intravenous injection of magnesium salts or IVR.

Interaction:

Contraindicated combinations (since the risk of developing a polymorphic ventricular tachycardia such as "pirouette" (torsade des pointes):

with antiarrhythmic agents IA class (quinidine, hydroquinidine, disopyramide, procainamide), Class III (dofetilide, ibutilide, brethil tosylate), sotalol;

others (not anti-arrhythmic drugs), such as beprideal, wincamine, some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants, cisapride, macrolides (erythromycin with intravenous administration, spiramycin), azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine (parenteral), dipemanyl methyl sulfate, misolastine, astemizole, terfenadine, fluoroquinolones incl. moxifloxacin.

Not recommended combinations:

with beta-blockers, some blockers of "slow" calcium channels (verapamil, diltiazem), because, may develop violations of automatism (bradycardia) and conduction;

with laxatives that can cause hypokalemia, which increases the risk of developing ventricular tachycardia of the typhus "pirouette" (tursade des pointes)

Combinations where caution should be exercised:

with drugs that cause hypokalemia (diuretics, systemic glucocorticosteroids, tetracosactide, amphotericin B (intravenously), t. possibly the development of ventricular tachycardia such as "pirouette" (torsade des pointes);

with anticoagulants of indirect action (warfarin) since Increased risk of bleeding as a result of increased concentrations of warfarin due to inhibition of isoenzyme CYP2C9 (it is necessary to monitor prothrombin and adjust the dose of anticoagulants);

with cardiac glycosides, tk. there may be violations of automatism (pronounced bradycardia) and disorders AV conductivity. In addition, it is possible to increase the concentration of digoxin in the blood plasma, by reducing its clearance (it is necessary to control the concentration of digoxin in the blood plasma, it requires clinical and ECG monitoring);

esmolol - violation of contractility, automatism and conduction (suppression of compensatory reactions of the sympathetic nervous system);

with phenytoin, fosphenitoin and cyclosporine - the risk of developing neurological disorders, it is possible to increase their concentration in the blood plasma by inhibiting the isoenzyme CYP2C9 (should monitor the concentration of phenytoin or cyclosporine in the blood plasma);

drugs metabolized with the participation of isoenzyme CYP3A4 (ciclosporin, fentanyl, lidocaine, tacrolimus, sildenafil, midazolam, triazolam, dihydroergotamine, ergotamine, statins, incl. simvastatin) - the risk of developing their toxicity and / or enhancing pharmacodynamic effects;

orlistat reduces the concentration of amiodarone and its active metabolite in the blood plasma;

clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine, neostigmine methylsulfate), pilocarpine - risk of development of severe bradycardia (cumulative effect);

Cholestyramine reduces absorption, elimination half-life and amiodarone concentration;

cimetidine slows the metabolism of amiodarone, which can cause an increase in the concentration of amiodarone in the blood plasma;

means for inhalation anesthesia and oxygen therapy increase the risk of developing bradycardia (resistant to atropine), arterial hypotension, conduction disorders, reduction of cardiac output, acute respiratory distress syndrome, incl. fatal, the development of which is associated with high concentrations of oxygen;

Amiodarone can suppress the absorption of sodium iodide (131-1, 123-1) and sodium pertechnetate (99mTc) of the thyroid gland, which can distort the results of the radioactive examination of the thyroid gland;

co-administration with lithium increases the risk of hypothyroidism; amiodarone increases the toxicity of methotrexate;

Rifampicin and preparations of St. John's wort (powerful isoenzyme inducers CYP3A4) reduce the concentration of amiodarone and desethylamiodarone in the blood serum (acceleration of metabolism in the liver);

Amiodarone slows the metabolism of budesonide, which as a result can lead to the development of Isenko-Cushing syndrome;

HIV protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir) increase the concentration of amiodarone in the blood serum, the risk of arrhythmias;

Clopidogrel - it is possible to reduce its plasma concentration;

dextromethorphan (substrate of isoenzymes CYP3A4 and CYP2D6) - it is possible to increase its concentration (amiodarone inhibits isoenzyme CYP2D6);

simvastatin (increased risk of side effects - dose-dependent) type of rhabdomyolysis. The dose of simvastatin should not exceed 20 mg per day. If a therapeutic effect can not be achieved at this dose, then another inhibitor of HMG-CoA reductase should be switched on, which does not enter into interactions of this type;

drugs that cause photosensitivity have an additive photosensitizing effect;

grapefruit juice increases AUC (the area under the concentration-time curve) and the maximum concentration (Cmah) of amiodarone by 50% and 84%, respectively;

increases the concentration in the blood plasma of quinidine, flecainide, procainamide and its metabolite N-acetylprocainamide.

Special instructions:

Before the start of treatment, and every 3 months, it is necessary to carry out ECG monitoring, while it should be taken into account that elderly patients have a more marked bradycardia, also necessary to conduct a radiological examination of the lungs, evaluate the function of the thyroid gland (hormones), liver (transaminases).

The frequency and severity of side effects depend on the dose of the drug, therefore, the minimum effective maintenance dose should be used.

When using Amiodarone, ECG changes are possible: lengthening of the interval QT with possible appearance of a prong U. When there is atrioventricular blockade of II and III degree, sinoatrial blockade, as well as blockade of the legs of the bundle, the treatment with Amiodarone should be stopped immediately.

Progressive dyspnoea and unproductive cough may be signs of lung damage. It is recommended to perform a chest X-ray and pulmonary functional tests (every 6 months and in case of clinical signs of pulmonary disease).

Before the start of therapy it is necessary to determine the content of plasma electrolytes.

During the period of Amiodarone treatment, the activity of liver enzymes is regularly monitored.

During the treatment period, ECG analysis is periodically performed (the width of the complex QRS and the duration of the interval QT), transaminase (with an increase of 3 times or doubling in the case of initially increased their activity dose reduced until the complete cessation of therapy).

In the process of treatment, an ophthalmological examination should be carried out (revealing significant deposits on the cornea and impaired vision require the withdrawal of Amiodarone).

In case of cancellation, recurrent rhythm disturbances are possible.

After the withdrawal of Amiodarone, the pharmacodynamic effect persists for 10-30 days.

The preparation contains iodine, so it can have effects on the results of tests of accumulation of radioactive iodine in the thyroid gland.Therefore, before the start of treatment, during its carrying out and for several months after the end of treatment, it is necessary to conduct research on the function of the thyroid gland.

Before the surgical interventions, as well as oxygen therapy, it is necessary to warn the doctor about the use of Amiodarone, as there were rare cases of development of acute respiratory distress syndrome in adults in the postoperative period.

To avoid the development of photosensitization, patients should avoid exposure to sunlight or use effective protective measures.

Caution should be exercised when using the drug during general anesthesia, there may be a risk of bradycardia, a marked decrease in blood pressure, conduction disorders, and a decrease in stroke volume of the heart.

Effect on the ability to drive transp. cf. and fur:

During the period of Amiodarone treatment, one should refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 200 mg.

Packaging:For 10 tablets in a planar cell package.For 30 tablets in a plastic can or in a polymer bottle. Each bank or vial, 3, 6 contour squares with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002389 / 01

Date of registration:22.04.2008

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Representation: & nbspNORTH STAR CJSC NORTH STAR CJSC Russia

Information update date: & nbsp11.09.2012

Illustrated instructions

Instructions

Amiodarone-SZ (Amiodarone-SZ)