Amiodarone, tablets 200 mg 30 pcs
€5.85 €5.12
Antiarrhythmic drug
ATX code [C01BD01]
Pharmacological properties
Pharmacodynamics./b>
Pharmacodynamics
A class III antiarrhythmic drug (repolarization inhibitor). It also has antianginal, coronarodilator, alpha- and beta-adreno-blocker and antihypertensive action.
Blocks inactivated potassium (to a lesser extent calcium and sodium) channels of cell membranes of cardiomyocytes. By blocking inactivated “fast” sodium channels, it has effects typical for class I antiarrhythmic drugs. Inhibits slow (diastolic) depolarization of sinus node cell membrane, causing bradycardia, inhibits atrioventricular (AV) conduction (effect of class IV antiarrhythmics).
It has the properties of a non-competitive blocker of alpha- and beta-adrenoceptors.
The antiarrhythmic action of amiodarone is associated with its ability to cause increase of the duration of action potential of cardiomyocytes and effective refractory period of atria and ventricles of heart, AV node, Gis bundle, Purkinje fibers which is accompanied with decrease of sinus node automatism, slowdown of AV conduction, decrease of cardiomyocytes excitability.
The antianginal action is caused by decrease of myocardial oxygen demand due to slowing of heart rate (HR) and decrease of coronary artery resistance, which leads to increase of coronary blood flow. There is no significant effect on systemic arterial pressure (BP).
In its structure it is similar to thyroid hormones. The iodine content is about 37% of its molecular weight. It affects thyroid hormone metabolism, inhibits conversion of thyroxine (T4) into triiodothyronine (TZ) (blockade of thyroxine-5-deiodinase) and blocks capture of these hormones by cardiac cells and hepatocytes, which leads to weakening of stimulating effect of thyroid hormones on myocardium.
The onset of action (even when using “loading” doses) is from 2-3 days to 2-3 months, the duration of action varies from several weeks to months (determined in plasma for 9 months after stopping its use).
Pharmacokinetics
Intake
After oral administration it is slowly absorbed from the gastrointestinal tract, bioavailability is 35-65%. It is detected in the blood after 1/2-4 hours. Maximum concentration in blood after a single dose is observed after 2-10 hours. The range of therapeutic plasma concentration is 1-2.5 mg/l (but in determining the dose it is necessary to take into account the clinical picture). Time to reach steady-state concentration (TCss) – from one to several months (depending on individual characteristics).
Distribution
The volume of distribution is 60 liters, indicating intense distribution in the tissues. It has high fat solubility, in high concentrations is found in adipose tissue and organs with good blood supply (concentrations in adipose tissue, liver, kidney, myocardium are higher than in blood plasma by 300, 200, 50 and 34 times respectively).
Peculiarities of pharmacokinetics of amiodarone determine the necessity of using the drug in high loading doses. It penetrates through blood-brain barrier and placenta (10-50 %), is secreted with breast milk (25 % of dose received by mother). Binding with plasma proteins is 95% (62% – with albumin. 33.5% – with beta-lipoproteins).
Metabolism
Metabolized in the liver; the main metabolite is desethylamiodarone, which has similar pharmacological properties, can enhance the antiarrhythmic effect of the main compound. It may also be metabolized by deiodination (about 9 mg of elemental iodine is excreted at a dose of 300 mg). With prolonged treatment, iodine concentrations can reach 60-80% of amiodarone concentrations. It is a carrier of organic anions, an inhibitor of P-glycoprotein and CYP2C9, CYP2D6 and CYP3A4, CYP3A5, CYP3A7, CYP1AI, CYP1A2 isoenzymes. CYP2C19, CYP2A6, CYP2B6, CYP2C8 in the liver.
With regard to the ability to cumulate and the associated large variability in pharmacokinetic parameters, data on the elimination half-life (T1/2) are inconsistent. Amiodarone excretion after oral administration occurs in two phases: the initial period is 4-21 hours, in the second phase the T1/2 is 25-110 days (on average 20-100 days). After prolonged oral administration, the average T1/2 is 40 days (this is important in dose selection because at least 1 month may be needed to stabilize new plasma concentrations, while complete elimination may take more than 4 months).
It is excreted through the intestine – 85-95%, by the kidneys – less than 1% of the ingested dose (so there is no need to change the dosage if renal function is impaired). Amiodarone and its metabolites are not subject to dialysis.
Indications
Prevention of recurrent paroxysmal rhythm disorders: life-threatening ventricular arrhythmias (including ventricular tachycardia and ventricular fibrillation); supraventricular arrhythmias (including in organic heart disease, as well as ineffectiveness or impossibility of other antiarrhythmic therapy); documented episodes of recurrent sustained supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome; atrial fibrillation and atrial flutter.
Prevention of sudden death due to arrhythmias in high-risk patients: patients after recent myocardial infarction with more than 10 ventricular extrasystoles per hour, with clinical signs of chronic heart failure (CHF) and left ventricular ejection fraction (LVEF) less than 40%.
Active ingredient
Amiodarone
Composition
Ingredients per tablet:
Active ingredient:
Amiodarone hydrochloride – 200,0 mg,
Excipients:
Lactose monohydrate – 100,0 mg,
Potato starch – 60,6 mg,
Microcrystalline cellulose – 24,0 mg,
How to take, the dosage
Tablets are taken orally with plenty of fluid.
The drug can be taken during or after a meal. The dosage regimen is established individually according to the patient’s condition and needs and is adjusted by the physician.
Loading (saturation) dose
In patients: the initial dose (divided into several (2-3) intakes) is 600-800 mg/day (up to the maximum dose of 1200 mg/day), until the total dose of 10 g (usually within 5-8 days).
Outpatient: The initial dose, divided into multiple doses, is 600-800 mg/day until a total dose of 10 g is reached (usually within 10-14 days).
Maintenance dose
In maintenance treatment, the lowest effective dose is used, depending on the patient’s individual response, and is usually between 100-400 mg/day. (
Due to the long period of semiejection the drug may be used every other day or there may be a two-day break during the week (5 days a week taking the therapeutic dose, with a two-day break at the end of the week). It is recommended to use the lowest loading and maintenance doses of the drug Amiodarone when treating elderly people.
Average therapeutic single dose is 200 mg, average therapeutic daily dose is 400 mg. The maximum single dose is 400 mg, the maximum daily dose is 1200 mg.
Interaction
Contraindicated combinations: risk of pirouette-type polymorphic ventricular tachycardia (arrhythmia characterized by polymorphic complexes that change the amplitude and direction of ventricular excitation relative to the isoline (electrical heart systole): Class IA antiarrhythmic agents (quinidine, hydroquinidine, disopyramide, procainamide), Class III (dofetilide, ibutilide, bretilium tozilate), sotalol; bepridil, vincamine, phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, thiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindol, pimozide tricyclic antidepressants, cisapride, macrolides (erythromycin IV, spiramycin), azoles, antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine (parenteral), difemanil methylsulfate, misolastine, astemizol, terfenadine, fluoroquinolones (incl.including moxifloxacin).
Unrecommended combinations: beta-adrenoblockers, blockers of “slow” calcium channels (verapamil, diltiazem) – the risk of impaired automatism (marked bradycardia) and conduction; laxatives stimulating peristalsis – the risk of ventricular tachycardia “pirouette” against hypokalemia caused by laxatives.
Combinations requiring use with caution: diuretics causing hypokalemia, amphotericin B (intravenous), systemic glucocorticosteroids, tetracosactide – risk of ventricular arrhythmias, including procainamide – risk of procainamide side effects (amiodarone increases the plasma concentration of procainamide and its metabolite -N-acetylprocainamide).
Indirect-acting anticoagulants (warfarin) – amiodarone increases warfarin concentration (risk of bleeding) due to inhibition of CYP2C9 isoenzyme; cardiac glycosides – impairment of automaticity (expressed bradycardia) and AV-conduction (increased concentration of digoxin).
Esmolol – impairment of contractility, automaticity and conduction (suppression of compensatory reactions of the sympathetic nervous system). Phenytoin, phosphenytoin – risk of neurological disorders (amiodarone increases phenytoin concentration due to inhibition of CYP2C9 isoenzyme).
Flecainide – amiodarone increases its concentration (due to inhibition of CYP2D6 isoenzyme).
Drugs that are metabolized with participation of CYP3A4 isoenzyme (cyclosporine, fentanyl, lidocaine, tacrolimus, sildenafil, midazolam, triazolam, dihydroergotamine, ergotamine, HMG-CoA reductase inhibitors) – amiodarone increases their concentrations (the risk of their toxicity and/or intensification of pharmacodynamic effects when coadministering amiodarone with high doses of simvastatin increases the risk of myopathy).
Orlistat decreases concentration of amiodarone and its active metabolite; clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine, neostigmine), pilocarpine – risk of severe bradycardia.
Cimetidine, grapefruit juice slow down amiodarone metabolism and increase its plasma concentration.
Inhaled drugs for general anesthesia – risk of bradycardia (resistant to atropine injection), acute respiratory distress syndrome, including fatal, the development of which is associated with high oxygen concentrations, risk of reduced blood pressure, cardiac output, conduction disorders.
Radioactive iodine – amiodarone (contains iodine) may interfere with the absorption of radioiodine, which may distort the results of radioisotope examination of the thyroid gland.
Rifampicin and St. John’s Wort (strong inducers of CYP3A4 isoenzyme) reduce the plasma concentration of amiodarone.
HIV – protease inhibitors (CYP3A4 isoenzyme inhibitors) can increase plasma concentrations of amiodarone.
Drugs that cause photosensitization have an additive photosensitizing effect.
Clopidogrel – its plasma concentration may decrease; dextromethorphan (substrate of CYP3A4 and CYP2D6 isoenzymes) – its concentration may increase (amiodarone inhibits CYP2D6 isoenzyme). Dabigatran – increase in its plasma concentrations in concomitant use with amiodarone.
Special Instructions
Caution should be exercised when prescribing the drug in patients with heart failure, liver disease, hypokalemia, porphyria, elderly patients.
Before treatment and every 6 months during therapy, it is recommended to check thyroid function, “hepatic” transaminase activity and to perform radiological examination of the lungs and consult an ophthalmologist. Control ECGs should be taken every 3 months.
Please note that Amiodarone may distort the results of determining the concentration of thyroid hormones (triiodothyronine, thyroxine, thyrotropic hormone).
If the heart rate is below 55 bpm, the drug should be temporarily stopped.
Amiodarone use may cause ECG changes: prolongation of QT interval with possible occurrence of U wave. If atrioventricular block of II and III degree, sinoatrial block, as well as Gis bundle branch block occur, treatment with Amiodarone should be stopped immediately.
Cancellation may lead to recurrence of cardiac rhythm disturbances. After drug withdrawal, pharmacodynamic effects persist for 10-30 days. Before surgical interventions as well as oxygen therapy it is necessary to warn a physician about use of Amiodarone, as there have been rare cases of acute respiratory distress syndrome in adult patients in the postoperative period.
In order to avoid photosensitization, patients should avoid Sun exposure. Deposition of lipofuscin in the corneal epithelium resolves on its own when the dose is reduced or Amiodarone is withdrawn. Skin pigmentation decreases after discontinuation of the drug and gradually (within 1-4 years) disappears completely. Spontaneous normalization of thyroid function is usually observed after discontinuation of treatment.
Information on possible effect on the ability to drive vehicles, machinery
When using the drug, one should refrain from driving and engaging in potentially dangerous activities requiring increased concentration and quick psychomotor reactions.
Synopsis
The tablets are white or white with a creamy tint, flat-cylindrical with a rib and a bevel.
Contraindications
Hypersensitivity to any of the drug components or iodine; sinus node weakness syndrome (sinus bradycardia and sinoatrial block in the absence of a pacemaker (risk of sinus node arrest); atrioventricular block of TI-III degree, two- and three-beam block (in the absence of a pacemaker); hypothyroidism, hyperthyroidism; severe arterial hypotension; lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome; hypokalemia, hypomagnesemia; interstitial lung disease; pregnancy, breastfeeding; concomitant use of monoamine oxidase inhibitors, QT interval prolongation drugs, congenital or acquired QT interval prolongation; age <18 years.
With caution
Chronic heart failure (CHF) (New York Heart Association (NYHA) Class III-IV functional class), Grade I atrioventricular block, liver failure, bronchial asthma, elderly (high risk of severe bradycardia).
If you have any of the conditions listed, always check with your doctor before using this medicine.
Side effects
Frequency: very common (10% or more), common (1% or more; less than 10%), infrequent (0.1% or more; less than 1%), rare (0.01% or more; less than 0.1%), very rare (less than 0.01%, including individual cases), frequency unknown (no data available to determine frequency).
Cardiovascular system disorders: Frequent – moderate bradycardia (dose-dependent); infrequent – sinoatrial and atrioventricular block of various degrees, proarrhythmogenic effect; very rare – severe bradycardia, sinus node arrest (in patients with sinus node dysfunction and elderly patients); frequency unknown – ventricular pirouette tachycardia, progression of chronic heart failure symptoms (with long-term use).
Digestive system disorders: very frequently – nausea, vomiting, decreased appetite, dulling or loss of taste, metallic taste in the mouth, sensation of heaviness in epigastrium, isolated increase of “liver” transaminases activity; frequently – acute toxic hepatitis with increased “liver” transaminases activity and/or jaundice, including development of liver failure; very rarely – chronic liver failure.
Respiratory system: often – interstitial or alveolar pneumonitis, obliterating bronchiolitis with pneumonia, pleurisy, pulmonary fibrosis; very rare – bronchospasm in patients with severe respiratory failure (especially in patients with bronchial asthma), acute respiratory syndrome; frequency is unknown – pulmonary bleeding.
Overlooking organ: very common – micro deposition in the corneal epithelium consisting of complex lipids, including lipofuscin (complaints of color halo or blurred contours of objects in bright light); very rare – optic neuritis/ optic neuropathy.
Metabolism disorders: often – hypothyroidism, hyperthyroidism; very rarely – syndrome of abnormal secretion of antidiuretic hormone.Skin disorders: very often – photosensitization; often – grayish or bluish pigmentation of the skin (with long-term use), which disappears after discontinuation of the drug; very rarely – erythema (with simultaneous radiation therapy), skin rash, exfoliative dermatitis (no relation with taking the drug), alopecia; frequency unknown – urticaria.
Nervous system disorders: frequently – tremor and other extrapyramidal disorders, sleep disturbances; infrequently – peripheral neuropathy and/or myopathy; very rarely – cerebellar ataxia, benign intracranial hypertension, headache.
Others: frequency unknown – angioneurotic edema, formation of granulomas, including bone marrow granulomas; very rare – vasculitis, epididymitis, impotence (relationship with taking the drug is not established), thrombocytopenia, hemolytic and aplastic anemia.
If you have any side effects, you should stop taking the medicine and see your doctor.
If any of the side effects listed in the instructions worsen, or if you notice any other side effects not listed in the instructions, tell your doctor.
Overdose
Symptoms: bradycardia, AV-blockade, pirouette-type ventricular tachycardia, pirouette-type paroxysmal tachycardia, exacerbation of symptoms of existing CHF, liver failure, cardiac arrest.
Treatment: gastric lavage, activated charcoal administration, symptomatic therapy (in bradycardia – beta-adrenergic pacemakers, atropine or pacemaker placement; in “pirouette” tachycardia – intravenous magnesium salt injection, cardiac pacing). Hemodialysis is ineffective.
Pregnancy use
Amiodarone should not be used during pregnancy, since during this period the thyroid gland of the newborn begins to cumulate iodine, and the use of Amiodarone during this period may provoke the development of hypothyroidism due to increased concentration of iodine. Administration during pregnancy and lactation is possible only in life-threatening rhythm disorders with ineffectiveness of other antiarrhythmic therapy, because the drug causes thyroid dysfunction of fetus.
Amiodarone penetrates through placenta (10-50%), is secreted with breast milk (25% of dose received by mother), so the drug is contraindicated for use during lactation. If it is necessary to use during lactation, breastfeeding should be stopped.
Similarities
Cordarone, Amiodarone
Weight | 0.350 kg |
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Shelf life | 2 years. Do not use after the expiration date stated on the package. |
Conditions of storage | In the dark place at a temperature not exceeding 25 ° C. Keep out of reach of children. |
Manufacturer | Ozon, Russia |
Medication form | pills |
Brand | Ozon |
Other forms…
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