Amiodarone pills 200mg, 30pcs

Composition

Composition 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, talc-7.0 mg, povidone (polyvinylpyrrolidone) – 4.8 mg, calcium stearate-3.6 mg

Pharmacological action

Antiarrhythmic agent

ATX code [C01BD01]

Pharmacological properties

Pharmacodynamics

Antiarrhythmic drug of class III (repolarization inhibitor). It also has antianginal, coronary dilating, alpha-and beta-adreno-blocking and antihypertensive effects.

Blocks non-activated potassium (to a lesser extent – calcium and sodium) channels of cardiomyocyte cell membranes. Blocking inactivated “fast” sodium channels, it has effects characteristic of Class I antiarrhythmic drugs. It inhibits slow (diastolic) depolarization of the sinus node cell membrane, causing bradycardia, and inhibits atrioventricular (AV) conduction (the effect of class IV antiarrhythmics).

It has the properties of a non-competitive blocker of alpha-and beta-adreno-receptors.

The antiarrhythmic effect of amiodarone is associated with its ability to cause an increase in the duration of the cardiomyocyte action potential and the effective refractory period of the atria and ventricles of the heart, AV node, Gis bundle, Purkinje fibers, which is accompanied by a decrease in the automatism of the sinus node, a slowdown in AV conduction, and a decrease in the excitability of cardiomyocytes.

The antianginal effect is caused by a decrease in the myocardial oxygen demand due to a decrease in the heart rate (HR) and a decrease in the resistance of the coronary arteries, which leads to an increase in coronary blood flow. It has no significant effect on systemic arterial pressure (BP).

It is structurally similar to thyroid hormones. The iodine content is about 37% of its molecular weight. It affects the exchange of thyroid hormones, suppresses the conversion of thyroxine (T4) to triiodothyronine (TZ) (thyroxine-5-deiodinase blockade) and blocks the uptake 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 the use of “loading” doses) is 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 use).

Pharmacokinetics

Suction

After oral use, it is slowly absorbed from the gastrointestinal tract, with a bioavailability of 35-65%. It is detected in the blood after 1/2-4 hours. The maximum concentration in the blood after taking a single dose is observed in 2-10 hours. The range of therapeutic plasma concentrations is 1-2.5 mg / l (but when determining the dose, it is necessary to keep in mind the clinical picture). The time to reach a steady-state concentration (TCSs) is from one to several months (depending on individual characteristics).

Distribution

The volume of distribution is 60 liters, which indicates an intensive distribution in the tissues. It has high fat solubility and is found in high concentrations in adipose tissue and organs with good blood supply (the concentration in adipose tissue, liver, kidneys, and myocardium is 300,200,50, and 34 times higher than in blood plasma, respectively).

Features of the pharmacokinetics of amiodarone necessitate the use of the drug in high loading doses. Penetrates the blood-brain barrier and placenta (10-50%), is secreted in breast milk (25% of the dose received by the mother). The relationship with plasma proteins is 95% (62% – with albumin. 33.5% – with beta-lipoproteins).

Metabolism

It is metabolized in the liver; the main metabolite, desethylamiodarone, which has similar pharmacological properties, can enhance the antiarrhythmic effect of the main compound. It may also be metabolized by deiodination (approximately 9 mg of elemental iodine is released at a dose of 300 mg). 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, CYP1AI, CYP1A2. CYP2C19, CYP2A6, CYP2B6, CYP2C8 in the liver.

Deduction

Given the ability to accumulate and the associated large variability in pharmacokinetic parameters, data on the half-life (T 1/2) are contradictory. Elimination of amiodarone after oral use is carried out in 2 phases: the initial period is 4-21 hours, in the second phase T 1/2-25-110 days (on average,20-100 days). After prolonged oral use, the average T 1/2 is 40 days (this is important when choosing the dose, since it may take at least 1 month to stabilize the new plasma concentration, while complete elimination may last more than 4 months).

It is excreted through the intestines – 85-95%, by the kidneys-less than 1% of the oral dose (therefore, with impaired renal function, there is no need to change the dosage). Amiodarone and its metabolites do not undergo dialysis.

Indications

Prevention of relapses of paroxysmal rhythm disorders:  life-threatening ventricular arrhythmias (including ventricular tachycardia and ventricular fibrillation); supraventricular arrhythmias (including in organic heart diseases, as well as when other antiarrhythmic therapy is ineffective or impossible); documented attacks of recurrent persistent supraventricular paroxysmal tachycardia in patients with Wolf-Parkinson-White syndrome; atrial fibrillation (fibrillation atrial fibrillation) and atrial flutter. Prevention of sudden death due to arrhythmia in high-risk patients:  patients after a recent myocardial infarction with the number of ventricular extrasystoles more than 10/h, with clinical signs of chronic heart failure (CHF) and a left ventricular ejection fraction (LV) of less than 40%.

Use during 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 during this period can provoke the development of hypothyroidism due to an increase in the concentration of iodine. Use during pregnancy and lactation is possible only in cases of life-threatening rhythm disorders with the ineffectiveness of other antiarrhythmic therapy, since the drug causes fetal thyroid dysfunction. Amiodarone passes through the placenta (10-50%), is secreted in 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, then breast-feeding should be discontinued.

Contraindications

Hypersensitivity to any of the components of the drug or iodine; sinus node weakness syndrome (sinus bradycardia and sinoatrial block in the absence of a pacemaker (risk of sinus node arrest); TI-III degree atrioventricular block, two – and three-bundle blocks (in the absence of a pacemaker); hypothyroidism, hyperthyroidism; severe arterial hypotension; lactose intolerance, lactase deficiency, glucose-galactose syndrome malabsorption; hypokalemia, hypomagnesemia; interstitial lung disease; pregnancy, breast-feeding; concomitant use of monoamine oxidase inhibitors, drugs that prolong the QT interval, congenital or acquired prolongation of the QT interval; age up to 18 years.

With caution

, chronic heart failure (CHF) (functional class III-IV according to the classification of chronic heart failure of the New York Heart Association-NYHA), atrioventricular block I degree, liver failure, bronchial asthma, old age (high risk of severe bradycardia).

If you have any of these conditions, be sure to consult your doctor before using the drug.

Side effects of

Frequency: very common (10% or more), often (1% or more; less than 10%), infrequently (0.1 percent or more; less than 1%), rare (0.01% or more; less than 0.1%), very rarely (less than 0.01%, including isolated cases), the frequency is unknown (according to the available data to determine the frequency is not possible).

From the cardiovascular system:  often-moderate bradycardia (dose-dependent); infrequently-sinoatrial and atrioventricular block of various degrees, proarrhythmogenic effect; very rarely-severe bradycardia, sinus node arrest (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, decreased appetite, bluntness or loss of taste sensations, metallic taste in the mouth, a feeling of heaviness in the epigastrium, isolated increase in the activity of “hepatic” transaminases; often – acute toxic hepatitis with increased activity of “hepatic” transaminases and/or jaundice, including the development of liver failure; very rarely – chronic liver failure.

Respiratory system disorders:  often-interstitial or alveolar pneumonitis, obliterating bronchiolitis with pneumonia, pleurisy, pulmonary fibrosis; very rarely-bronchospasm in patients with severe respiratory insufficiency (especially in patients with bronchial asthma), acute respiratory syndrome; frequency unknown – pulmonary bleeding.

From the side of the visual organ: very often – microdeposits in the corneal epithelium, consisting of complex lipids, including lipofuscin (complaints of the appearance of a colored halo or blurred contours of objects in bright light); very rarely-optic neuritis/visual neuropathy.

From the side of metabolism: often – hypothyroidism, hyperthyroidism; very rarely – syndrome of impaired secretion of antidiuretic hormone. From the side

of the skin: very often – photosensitization; often-grayish or bluish pigmentation of the skin (with prolonged use), disappears after discontinuation of the drug; very rarely-erythema (with simultaneous radiation therapy), skin rash, exfoliative dermatitis (no connection with taking the drug has been established), alopecia; frequency unknown-urticaria.

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

Other services: the frequency is unknown-angioedema, granuloma formation, including bone marrow granulomas; very rarely-vasculitis, epididymitis, impotence (the relationship with taking the drug is not established), thrombocytopenia, hemolytic and aplastic anemia.

If side effects occur, you should stop using the drug and consult a doctor. If any of the side effects listed in the instructions get worse or you notice any other side effects that are not listed in the instructions, tell your doctor.

Interaction

Contraindicated combinations: risk of developing polymorphic ventricular tachycardia of the “pirouette” type (arrhythmia characterized by polymorphic complexes that change the amplitude and direction of excitation through the ventricles relative to the isoline (electrical systole of the heart): antiarrhythmic agents of class IA (quinidine, hydroquinidine, disopyramide, procainamide), Class III (dofetilide, ibutilide, bretilia tosylate), sotalol; bepridil, vincamine, phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazii, fluphenazii), benzamides (amisulpride, sultopride, sulpiride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), sertindol, pimozide; tricyclic antidepressants, cisapride, macrolides (intravenous erythromycin, spiramycin), azoles, antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine (parenterally), difemanyl methylsulfate, mizolastine, astemizole, terfenadine, fluoroquinolones (including moxifloxacin). Not recommended combinations: beta-blockers, slow calcium channel blockers (verapamil, diltiazem) – the risk of automatism disorders (pronounced bradycardia) and conduction; laxatives that stimulate intestinal motility – the risk of developing ventricular tachycardia of the “pirouette” type against the background of hypokalemia caused by laxatives. Combinations that need to be used with caution: diuretics that cause hypokalemia, amphotericin B (intravenously), systemic glucorticosteroids, tetracosactide – the risk of ventricular arrhythmias, including ventricular tachycardia of the “pirouette” type; procainamide – the risk of developing side effects of procainamide (amiodarone increases the plasma concentration of procainamide and its metabolite-N-acetylprokainamide). Indirect anticoagulants (warfarin – – amiodarone increases the concentration of warfarin (risk of bleeding) due to inhibition of the CYP2C9 isoenzyme; cardiac glycosides-violation of automatism (severe 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 – risk of neurological disorders (amiodarone increases the concentration of phenytoin by inhibiting the CYP2C9 isoenzyme). Flecainide-amiodarone increases its concentration (due to inhibition of the CYP2D6 isoenzyme). Drugs that are metabolized with the participation of the CYP3A4 isoenzyme (cyclosporine, fentanyl, lidocaine, tacrolimus, sildenafil, midazolam, triazolam, dihydroergotamine, ergotamine, HMG-CoA reductase inhibitors) – amiodarone increases their concentration (the risk of their toxicity and/or increased pharmacodynamic effects when taking amiodarone with high doses of simvastatin increases the likelihood of developing myopathy). Orlistat reduces the concentration of amiodarone and its active metabolite; clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine, neostigmine), pilocarpine – the risk of severe bradycardia. Cimetidine, grapefruit juice slow down the metabolism of amiodarone and increase its plasma concentration. Inhaled medications for general anesthesia – the risk of developing bradycardia (resistant to atropine), acute respiratory distress syndrome, including fatal, the development of which is associated with high oxygen concentrations, the risk of lowering blood pressure, cardiac output, and conduction disorders. Radioactive iodine-amiodarone (contains iodine in its composition) can interfere with the absorption of radioactive iodine, which can distort the results of a radioisotope study of the thyroid gland. Rifampicin and St. John’s wort preparations (strong inducers of the CYP3A4 isoenzyme) reduce the concentration of amiodarone in blood plasma. HIV protease inhibitors (inhibitors of the CYP3A4 isoenzyme) – may increase plasma concentrations of amiodarone. Drugs that cause photosensitization have an additive photosensitizing effect. Clopidogrel – may decrease its plasma concentration; dextromethorphan (substrate of CYP3A4 and CYP2D6 isoenzymes) – may increase its concentration (amiodarone inhibits the CYP2D6 isoenzyme). Dabigatran – an increase in its concentration in blood plasma when used simultaneously with amiodarone.

How to take, course of use and dosage

Use Amiodarone only as directed by your doctor!Tablets are taken orally, washed down 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. Loading (saturating) dose in the hospital: the initial dose (divided into several (2-3) doses) is 600-800 mg/day (up to a maximum dose of 1200 mg / day), until a total dose of 10 g is reached (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). Maintenance dose In maintenance treatment, the lowest effective dose is used depending on the individual response of the patient and usually ranges from 100-400 mg / day (1/2-2 tablets) in 1-2 doses. Due to the long half-life, the drug can be used every other day or take a break from taking it 2 days a week (taking the therapeutic dose of the drug for 5 days a week, with a break for 2 days at the end of the week). In the treatment of the elderly, it is recommended to use the lowest loading and maintenance doses of 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.

Overdose

Symptoms: bradycardia, AV block, ventricular tachycardia of the “pirouette” type, paroxysmal tachycardia of the “pirouette” type, worsening of the symptoms of existing CHF, impaired liver function, cardiac arrest. Treatment: gastric lavage, taking activated charcoal, symptomatic therapy (for bradycardia – beta-adrenostimulants, atropine or pacemaker installation; for pirouette-type tachycardia-intravenous use of magnesium salts, pacing). Hemodialysis is ineffective.

Description

Tablets of white or white with a creamy tint of color are flat-cylindrical with a risk and chamfer.

Special instructions

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

Before starting treatment and every 6 months during therapy, it is recommended to check the function of the thyroid gland, the activity of” liver ” transaminases, and conduct an X-ray examination of the lungs and consult an optometrist. Control ECGs should be taken every 3 months.

It should be borne in mind that when using Amiodarone, the results of determining the concentration of thyroid hormones (triiodothyronine, thyroxine, thyroid-stimulating hormone) may be distorted.

If the heart rate is below 55 beats / min, the drug should be temporarily discontinued.

When using the drug Amiodarone, ECG changes are possible: prolongation of the QT interval with the possible appearance of the U-wave. If grade II and III atrioventricular block, sinoatrial block, or bundle branch block occurs, treatment with Amiodarone should be discontinued immediately.

If canceled, relapses of cardiac arrhythmias may occur. After discontinuation of the drug, the pharmacodynamic effect persists for 10-30 days. Before performing surgical interventions, as well as oxygen therapy, it is necessary to warn the doctor about the use of Amiodarone, since there have been rare cases of acute respiratory distress syndrome in adult patients in the postoperative period.

To avoid photosensitization, patients should avoid exposure to the sun. The deposition of lipofuscin in the corneal epithelium decreases independently when the dose is reduced or Amiodarone is discontinued. Skin pigmentation 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.

Information about possible effects on the ability to drive vehicles and mechanisms

During the treatment period, you should refrain from driving a vehicle and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

In a dark place at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Amiodarone

Conditions of release from pharmacies

By prescription

Dosage form

Tablets