Amiodarone - instructions for use, doses, side effects, contraindications

Lactose monohydrate - 100.0 mg, potato starch - 60.6 mg, microcrystalline cellulose - 24.0 mg, talc - 7.0 mg, povidone (polyvinylpyrrolidone) - 4.8 mg, calcium stearate - 3.6 mg.

Description:

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

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-adrenoceptive and antihypertensive action.

Blocks unactivated potassium (to a lesser extent - calcium and sodium) channels of cardiomyocyte cell membranes. Blocking inactivated "fast" sodium channels, 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 the atrioventricular (AV) carrying out (effect antiarrhythmics IV class).

Has the properties of a non-competitive blocker of alpha- and beta-adrenergic receptors.

The antiarrhythmic effect of amiodarone is related to its ability to tear out the prolongation of the cardiomyocyte action potential and the effective refractory period of the atria and ventricles of the heart, the AV node, the bundle of His, Purkinje fibers,which is accompanied by a decrease automatism of the sinus node, slowing of AV-conduction, decrease in excitability of cardiomyocytes.

AntiangianThis effect is due to a decrease in myocardial oxygen demand due to a decrease in the heart rate (heart rate) and a decrease in the resistance of the coronary arteries, which leads to an increase in coronary blood flow. Has no significant effect on systemic blood pressure (BP).

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 conversion of thyroxine (T4) to triiodothyronine (T3) (blockade of thyroxine-5-deiodinase) and blocks the seizure of these hormones by cardiocytes and hepatocytes, which leads to a weakening of the stimulating effect of thyroid hormones on the myocardium.

The onset of action (even with "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:

Suction

After oral administration, it is slowly absorbed from the gastrointestinal tract, bioavailability is 35-65%. It is found in the blood after 1 / 2-4 hours.The maximum concentration in the blood after taking a single dose is observed after 2-10 hours. The range of therapeutic plasma concentration is 1-2.5 mg / l (but when determining the dose, it is necessary to have a clinical picture). Time to reach a stationary concentration (TCss) - from one to several months (depending on individual characteristics).

Distribution

The volume of distribution is 60 liters, which indicates an intensive distribution in tissues. 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 blood 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 and 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).

Metabolism

Metabolised in the liver; the main metabolite, desethylamiodarone, which has similar pharmacological properties, can enhance the antiarrhythmic effect of the basic compound.Perhaps, it is also metabolized 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 concentration of amiodarone. It is a carrier of organic anions, inhibitor of P-glycoprotein and isoenzymes CYP2C9, CYP2D6 and CYP3A4, CYP3A5, CYP3A7, CYP1A1, CYP1A2, CYP2C19, CYP2A6, CYP2B6, CYP2C8 in the liver.

Excretion

Taking into account the ability to accumulate and the large variability of pharmacokinetic parameters associated with this, the data on the half-life period (T1 / 2) are inconsistent. Removal of amiodarone after ingestion is carried out in 2 phases: the initial period is 4-21 hours, in the second phase of T1 / 2 - 25-110 days (an average of 20-100 days). After long ingestion, the average T1 / 2 is 40 days (this is important in choosing a dose, since it may take at least 1 month to stabilize the new plasma concentration, while the complete elimination may last for more than 4 months) .

Output through the intestine - 85-95%, kidneys - less than 1% of the dose taken internally (therefore, if there is impaired renal function, there is no need to change the dosage). Amiodarone and its metabolites are not dialyzed.

Indications:

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

Preventing sudden death due to arrhythmia in patients at high risk: patients after recent myocardial infarction with ventricular extrasystoles amount of more than 10 / h, with clinical signs of congestive heart failure (CHF) and left ventricular ejection fraction (LV) of less than 40%.

Contraindications:

Hypersensitivity to any of the components of the drug or iodine; sick sinus syndrome (sinus bradycardia and sinoatrial block without pacemaker (risk of cardiac sinus); atrioventricular block II-III degree two and Three-beam blockade (in the absence of the pacemaker); hypothyroidism,hyperthyroidism; severe arterial hypotension; lactose intolerance, lactase deficiency, glucose-galactose mapping syndrome; hypokalemia, hypomagnesemia; interstitial lung disease; pregnancy, the period of breastfeeding; simultaneous administration of monoamine oxidase inhibitors, drugs prolonging the QT interval, congenital or acquired prolongation of the QT interval; age to 18 years. For additional information see the section "Interaction with other medicinal products".

Carefully:

Chronic heart failure (CHF) (III-IV functional class on the classification of chronic heart failure of the New York Association of Cardiologists - NYHA), atrioventricular blockade of the I degree, hepatic insufficiency, bronchial asthma, elderly age (high risk of severe bradycardia).

If you have any of the listed diseases, always consult a doctor before using the drug.

Pregnancy and lactation:Do not use Amiodarone during pregnancy, because during this period the thyroid gland of the newborn begins to accumulate iodine, and the use of Amiodarone in this period can provoke the development of hypothyroidism due to an increase in the concentration of iodine. Application in pregnancy and during lactation is possible only with life-threatening rhythm disturbances with the inefficiency of other antiarrhythmic therapy, as the drug causes dysfunction of the thyroid of the fetus. Amiodarone penetrates the placenta (10-50%), is secreted with breast milk (25% of the dose received by the mother), so the drug is contraindicated for use during lactation. If it is necessary to use during lactation, breastfeeding should be abolished.

Dosing and Administration:

A drug Amiodarone Apply only as directed by a doctor!

Tablets are taken orally by washing with a sufficient amount of liquid. The drug can be taken during or after a meal. The dosage regimen is set individually in accordance with the patient's condition and needs and is adjusted by the doctor.

The loading (saturating) dose

Inpatient: the initial dose (divided into several (2-3) receptions) is 600-800 mg / day (up to a maximum dose of 1200 mg / day), until a total dose of 10 g (usually within 5-8 days).

Outpatient: The initial dose divided into several doses is 600-800 mg / day until a total dose of 10 g is reached (usually within 10-14 days).

Supporting 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 / 2-2 tablets) in 1-2 divided doses.

Due to the long half-life, the drug can be used after a day or take a break in taking 2 days a week (taking a therapeutic dose of the drug for 5 days a week, with a break for a day at the end of the week). In the treatment of the elderly, it is recommended to use the least load and maintenance doses of the drug Amiodarone.

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 available data, it is not possible to determine the frequency).

Co cardiovascular system: often - moderate bradycardia (dose-dependent); infrequently - sinoatrial and atrioventricular blockade of various degrees, proarrhythmogenic action; very rarely - severe bradycardia, stopping the sinus node (in patients with sinus node dysfunction and elderly patients); frequency unknown - ventricular tachycardia of the "pirouette" type, progression of symptoms of chronic heart failure (with prolonged use).

From the digestive system: very often - nausea, vomiting, loss of appetite, dullness or loss of taste, metallic taste in the mouth, a feeling of heaviness in the epigastrium, an isolated increase in the activity of "liver" transaminases; often acute toxic hepatitis with an increase in the activity of "liver" transaminases and / or jaundice, including the development of hepatic insufficiency; very rarely - chronic liver failure.

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

From the side of the organ of vision: very often - microdeposition in the epithelium of the cornea, consisting of complex lipids, including lipofuscin (complaints of the appearance of a halo or fuzziness of contours of objects in bright light); very rarely - optic neuritis / visual neuropathy. From the side of metabolism: often - hypothyroidism, hyperthyroidism; very rarely - the syndrome of impaired secretion of antidiuretic hormone.

From the skin: very often - photosensitivity; often - grayish or bluish skin pigmentation (with prolonged use), disappears after discontinuation of the drug; very rarely - erythema (with simultaneous radiotherapy), skin rash, exfoliative dermatitis (ligament is not established), alopecia; frequency unknown - hives.

From the nervous system: often - tremor and other extrapyramidal disorders, sleep disturbance; infrequently peripheral neuropathy and / or myopathy; very rarely - cerebellar ataxia, benign intracranial hypertension, headache.

Other: frequency unknown - angioedema, education granulomas, including bone marrow granulomas; Very rarely - vasculitis, epididymitis, impotence (there is no connection with taking the drug), trebocytopaedy, hemolytic and aplastic anemia.

In case of adverse reactions, it is necessary to cancel the drug and consult a doctor.

If any of the side effects indicated in the manual are aggravated or you notice any other side effects not indicated in the instructions, inform the doctor about it.

Overdose:

Symptoms: bradycardia, AV-blockade, ventricular tachycardia of the "pirouette" type, paroxysmal tachycardia of the "pirouette" type, aggravation of the symptoms of the available XCN, impaired liver function, cardiac arrest.

Treatment: gastric lavage, intake of activated charcoal, symptomatic therapy (with bradycardia - beta-adrenostimulyagory, atropine or installation of a pacemaker; with tachycardia of the type "pirouette" - iv administration of magnesium salts, pacing). Hemodialysis is ineffective.

Interaction:

Contraindicated combinations: risk of developing polymorphic ventricular tachycardia such as "pirouette" (arrhythmia,characterized by polymorphic complexes that change the amplitude and direction of excitation through the ventricles relative to the isoline (electric heart systole): antiarrhythmics IA class (quinidine, hydroquinidine, disopyramide, procainamide), III class (dofetilide, ibutilide, brethil tosylate), sotalol; beprideil, wincamine, phenothiazines (chlorpromazine, scammazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiapride, verialidide), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants, cisapride, macrolides (erythromycin in / in, spiramycin), azoles, antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine (parenteral), dipemanyl methyl sulfate, misolastine, astemizole, tefenadine, fluoroquinolones (incl. moxifloxacin).

Uncommon combinations: beta-blockers, blockers "slow" calcium channels (verapamil, diltiazem) - the risk of violation of automatism (pronounced bradycardia) and conduction; laxatives,stimulating peristalsis of the intestine - the risk of developing a ventricular tachycardia such as "pirouette" against hypokalemia caused by laxatives.

Combinations requiring use with caution: diuretics that cause hypokalemia, amphotericin B (intravenously), systemic glucocorticosteroids, tetracosactide - risk of developing ventricular fissures of the rhythm, incl. ventricular tachycardia of the "pirouette" type; procainamide - risk of side effects of procainamide (amiodarone increases the plasma concentration of procainamide and its metabolite - N-acetyl procainamide).

Anticoagulants of indirect action (warfarin) - amiodarone increases the concentration of warfarin (risk of bleeding) due to inhibition of the isoenzyme CYP2S9; cardiac glycosides - a violation of automatism (pronounced bradycardia) and AV-conduction (increased digoxin concentration).

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

Phenytoin, phosphenytoin - the risk of developing neurological disorders (amiodarone increases the concentration of phenytoin by inhibiting the enzyme CYP2C9).

Flecainide - amiodarone increases its concentration (due to inhibition of the enzyme CYP2D6).

Drugs metabolized with the participation of the isoenzyme CYP3A4 (ciclosporin, fentanyl, lidocaine, tacrolimus, sildenafil, miidazoles, triazolam, dihydroergotamine, ergotamine, HMG-CoA reductase inhibitors) - amiodarone increases their concentration (the risk of developing their toxicity and / or enhancing pharmacodynamic effects with the simultaneous administration of amiodarone with high doses of simvastatin increases the likelihood of myopathy).

Orlistat reduces the concentration of amiodarone and its active metabolite; onidin, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridosigmine, neosigmine), pilocarpine - risk of development of severe bradycardia.

Cimetidine, grapefruit juice slows the metabolism of amiodarone and increases its plasma concentration.

Inhaled drugs for general anesthesia - the risk of developing bradycardia (resistant to atropine), acute respiratory distress syndrome, incl. fatal, the development of which is associated with high concentrations of oxygen, the risk of lowering blood pressure,cardiac output, conduction disorders.

Radioactive iodine - amiodarone (contains in its composition iodine) can disrupt the absorption of radioactive iodine, which can distort the results of a radioisotope study of the thyroid gland.

Rifampicin and preparations of St. John's wort (strong inducers and: the enzyme CYP2A4) reduce the concentration of amiodarone in the blood plasma.

HIV-protease inhibitors (inhibitors of the isoenzyme CYP3A4) - can increase plasma concentrations of amiodarone.

Medicines that cause photosensitivity have an additive photosensitizing effect.

Clopidogrel - it is possible to reduce its plasma concentration; dextromethorphan (a substrate of isoenzymes CYP3A4 and CYP2D6) - it is possible to increase its concentration (amiodarone inhibits the isoenzyme CYP2D6). Dabigarran - increase in its concentration in blood plasma with simultaneous application with amiodarone.

Special instructions:

Care should be taken when prescribing the drug to patients with heart failure, liver disease, hypokalemia, porphyria, and elderly patients.

Before the start of treatment and every 6 months during therapy, it is recommended to check the function of the thyroid gland,activity of "liver" transaminases and to conduct an x-ray examination of the lungs and consultation of the oculist. Control ECG should be removed every 3 months. It should be borne in mind that against the background of the application of Amiodarone, the results of determining the concentration of thyroid hormones (triiodothyronine, thyroxine, thyrotropic hormone) may be distorted.

If the heart rate is lower than 55 y / d, the drug should be temporarily canceled.

When using the drug Amiodarone ECG changes possible: lengthening of the interval QT with possible appearance of a prong U. With the appearance of atrioventricular blockade of II and III degree, sinoatrial blockade, as well as blockade of the legs of the bundle, the treatment with the drug Amiodarone should be stopped immediately. With the cancellation of a possible recurrence of heart rhythm disturbances. After the drug is discontinued, the pharmacodynamic effect persists for 10-30 days. Before carrying out surgical interventions, as well as oxygen therapy, it is necessary to warn the doctor about the use of the drug Amiodarone, because there were rare cases of development of acute respiratory distress syndrome in adult patients in the postoperative period.

Boo avoid the development of photosensitivity patients should avoid exposure to the sun. The deposition of lipofuscin in the epithelium of the cornea decreases independently when the dose is lowered or Amiodarone is withdrawn. Pigmentation of the skin decreases after discontinuation of the drug and gradually (within 1-4 years) completely disappears. After discontinuation of treatment, as a rule, spontaneous normalization of thyroid function is observed.

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

During the treatment period, one should refrain from driving a vehicle 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.

2, 3 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In the dark 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003074

Date of registration:06.07.2015

Expiration Date:06.07.2020

The owner of the registration certificate:ALTAYVITAMINS, CJSC ALTAYVITAMINS, CJSC Russia

Manufacturer: & nbsp

ALTAYVITAMINS, CJSC Russia

Information update date: & nbsp12.08.2017

Illustrated instructions

Instructions

Amiodarone (Amiodaron)