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

Excipients: potato starch, microcrystalline cellulose, magnesium stearate, crospovidone (Kollidon CL-M), silicon dioxide colloid, hypromellose (hydroxypropylmethylcellulose).

Description:

Tablets from white to white with a grayish or creamy hue of color, flat-cylindrical, with a facet and a risk. A slight "marble" is allowed.

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 slow (diastolic) depolarization of the membrane of the cells of the sinus node, causing bradycardia and a decrease AV conductivity.

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; reduces the heart rate; It increases the energy reserves of the myocardium (by increasing the content kreatinsulfata, adenosine and glycogen).

It is similar in its structure to thyroid hormones. The iodine content is about 37% of its molecular weight. Influences the metabolism of thyroid hormones, inhibits T3 conversion of T4 (block thyroxine-5-deiodinase) 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 (T3 deficiency may bring to its overproduction and hyperthyroidism). The onset of action (even with the use of "loading" doses) - from 2-3 days to 2-3 months, duration of action ranging from several weeks to months (as determined in plasma for 9 months after the cessation of his reception).

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 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 (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 concentration 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 prolonged oral administration, the mean T1 / 2 is 40 days (this is important in the choice of dose, since it may be necessary for at least 1 month to stabilize the new plasma concentration, while complete elimination may last longer 4 months). It is excreted in the 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 dosage). Amiodarone and its metabolites are not dialyzed.

Indications:

- Treatment and prevention of heart rhythm disorders associated with Wolff-Parkinson-White syndrome (WPW), paroxysms of flicker and atrial flutter; atrial and ventricular extrasystole; parasystole, ventricular arrhythmias in patients with Chagas myocarditis;

- prevention of recurrent ventricular and atrial fibrillation; treatment of ventricular tachycardia;

- treatment of supraventricular tachycardia in order to restore sinus rhythm with flicker and atrial flutter;

- in the period of rehabilitation after myocardial infarction, if there is an indication in the anamnesis of previously noted episodes of arrhythmia.

Contraindications:

- Hypersensitivity to iodine, to amiodarone or to other components of the drug;

- sinus bradycardia and sinoatrial block;

- syndrome of weakness of the sinus node (in the absence of a pacemaker);

- atrioventricular blockade of II - III degree, violations of intraventricular conduction (two- and three-beam blockades) in the absence of a pacemaker;

- cardiogenic shock, collapse, severe arterial hypotension;

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

- pregnancy and lactation (breastfeeding);

- simultaneous reception with drugs that can cause polymorphic ventricular tachyarrhythmia such as "pirouette" (torsade de pointe);

- antiarrhythmics IA class (quinidine, disopyramide); antiarrhythmic drugs of III class (sotalol, dofetilide, ibutilide); beprideil;

- other (non-antiarrhythmic) drugs, such as, wincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sultopride, sulpride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide); cisapride; macrolide antibiotics, in particular erythromycin with intravenous administration, spiramycin; azoles; pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine);

- hypokalemia;

- severe heart failure;

- interstitial lung diseases;

- simultaneous administration of monoamine oxidase inhibitors (MAO);

- age to 18 years (efficacy and safety not established).

Carefully:

Care should be taken when using the drug in patients with hepatic insufficiency, bronchial asthma, in elderly patients (high risk of severe bradycardia), chronic heart failure, atrioventricular blockade of the I degree.

Pregnancy and lactation:

Contraindicated in the II and III trimester of 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 iodine concentration.

Amiodarone is excreted in breast milk in a significant amount, so the drug is contraindicated for use during lactation.

Dosing and Administration:

Tablets are taken internally during or after a meal, with a sufficient amount of liquid.

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

The saturation dose is 600 mg / day (3 tablets), divided into 2-3 doses. The course of treatment is 8-15 days. If necessary, the dose of Amiodarone-Acry can be increased to 800-1200 mg / day (4-6 tablets), for a short period and under ECG monitoring. After reaching the signs of saturation, they switch to maintenance therapy.

Supportive dose. With maintenance treatment, the lowest effective dose is used depending on the individual reaction of the patient and usually ranges from 200-400 mg / day (1-2 tablets) in 1-2 divided doses. In cases where it is possible every 5 days of taking the drug make a two-day break.

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:

From the sense organs: uveitis, 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 are possible about the appearance of color halos or fuzziness of the contours), in rare cases, a retinal microcellular retina, optic neuritis.

From the skin: vasculitis, photosensitivity (skin hyperemia), lead-blue or bluish skin pigmentation (with prolonged use), after discontinuation of treatment slowly disappears within 10-14 days, alopecia.

From the endocrine system: increase in T4 levels with normal or slightly decreased T3 (in the absence of clinical signs of thyroid dysfunction, treatment should not be discontinued). With long-term use, it is possible to develop in rare cases - hypothyroidism, much less often hyperthyroidism (it is necessary to cancel the drug). Possible development of the syndrome of inadequate secretion of antidiuretic hormone.

From the respiratory system: with prolonged use - cough, dyspnea, alveolar and / or interstitial pneumonitis, pneumonia, pulmonary fibrosis, pleurisy, apnea, bronchospasm (especially in patients with severe respiratory failure or bronchial asthma), acute respiratory distress syndrome, sometimes fatal and sometimes immediately after surgery (the possibility of interaction with high doses of oxygen is assumed), pulmonary hemorrhage (the frequency is unknown).

From the central and peripheral nervous system: headache, general weakness, dizziness, depression, fatigue, paresthesia, auditory hallucinations, with long-term use - peripheral neuropathy, myopathy (symptoms reversible after drug discontinuation), tremor, memory impairment, sleep, extrapyramidal disorders; cerebellar ataxia, benign intracranial hypertension (pseudotumour of the brain) - very rarely.

From the digestive system: nausea, vomiting, taste disorder, constipation, flatulence, diarrhea, pain in the epigastric region, with prolonged use - toxic hepatitis, cholestasis, cirrhosis, hepatic insufficiency.

Allergic reactions: skin rash, including exfoliative dermatitis, angioedema (frequency unknown).

From the cardiovascular system: sinus bradycardia (refractory to anticholinergics); sinoatrial blockade, AV blockade, "tides" of blood to the skin of the face, arrhythmogenic effect, with prolonged use - progression of symptoms of chronic heart failure, tachycardia such as pirouette, weighting of the current of the existing arrhythmia or its occurrence.

Laboratory indicators: rarely - increased activity of "liver" transaminases, with prolonged use - thrombocytopenia, hemolytic and aplastic anemia. Other: rarely epididymitis, decreased libido, a violation of potency, vasculitis, kidney damage with an increase in the level of creatinine.

Overdose:

In the case of the appearance of toxicity in the form of arrhythmogenic effect, the drug is canceled.

Symptoms: lowering of arterial pressure, sinus bradycardia, arrhythmias, atrioventricular blockade, violations of liver function.

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, the appointment of atropine, beta1-adrenostimulants, in severe cases - pacing.

Interaction:

Amiodarone interacts with a large number of drugs. Because of the long half-life, the possibility of the emergence of interactions exists not only with concomitantly used drugs, but also with drugs that will be used after discontinuing amiodarone therapy.

Contraindicated combinations:

- with drugs that can cause a polymorphic ventricular tachycardia such as "pirouette";

antiarrhythmic agents IA class (quinidine, disopyramide); antiarrhythmic drugs of III class (sotalol, dofetilide, ibutilide); Bepridilom (when combined with amiodarone, the risk of ventricular tachycardia increases, in particular potentially lethal ventricular pirouette tachycardia, and the predisposition to sinus bradycardia, blockade of the sinus node, and impaired AV conductivity);

- other (not anti-arrhythmic) drugs, such as, wincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sultopride, sulpride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide); cisapride; macrolide antibiotics, in particular erythromycin with intravenous administration, spiramycin; azoles; pentamidine with parenteral administration; diphenamyl methyl sulfate; Misolastine (when combined with amiodarone, the risk of ventricular tachycardia increases, in particular potentially lethal ventricular pirouette tachycardia);

- with MAO inhibitors.

Not recommended combinations:

- with halofantrine, pentamidine, astemizole, terfenadine, lumefantrine, tricyclic antidepressants, since it is possible to lengthen the interval QT, which increases the risk of developing ventricular arrhythmias, in particular tachycardia such as "pirouette";

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

- with laxatives that can cause hypokalemia, as the risk of developing ventricular tachycardia such as "pirouette" (torsade de pointe);

- with fluoroquinolones (in particular moxifloxacin) - the lengthening of the interval is possible QT.

Combinations where caution should be exercised:

- with drugs that cause hypokalemia (diuretics, systemic glucocorticosteroids, tetracosactide, pentamidine, amphotericin B (intravenously), since it is possible to develop ventricular tachycardia such as "pirouette" (torsade de pointe);

- with anticoagulants for oral administration, as the risk of bleeding increases (it is necessary to monitor the level of prothrombin and adjust the dose of anticoagulants);

- with cardiac glycosides, since there may be abnormalities of automatism (manifested by bradycardia) and violations of atrioventricular conduction. In addition, it is possible to increase the concentration of digoxin in the blood plasma by reducing its clearance (it is necessary to monitor the concentration of digoxin in the blood plasma, ECG - control);

- with phenytoin, cyclosporin, an increase in their concentration in the blood plasma is possible (the concentration of phenytoin or cyclosporin in the blood plasma should be monitored);

- colestramine reduces absorption, half-life and concentration of amiodarone; cimetidine slows the metabolism of amiodarone, which can cause an increase in the concentration of amiodarone in the blood plasma;

- funds for inhalation anesthesia, oxygen therapy increase the risk of developing bradycardia (resistant to atropine), arterial hypotension, conduction disturbance, decrease in IOC;

- amiodarone can suppress the absorption of sodium iodide (131-1, 123-1) and sodium pertechnetate (99mTc) of the thyroid gland;

- combined use with lithium increases the risk of hypothyroidism;

- amiodarone increases the toxicity of methotrexate;

- rifampicin reduces the level of amiodarone in the blood serum (acceleration of metabolism in the liver);

- amiodarone slows the metabolism of budesonide, which as a result can lead to the appearance of Cushing's syndrome;

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

- simvastatin (increased risk of side effects, dose-dependent) such as rhabdomyolysis. The dose of simvastatin should not exceed 20 mg per day. If, at such a dose, the therapeutic effect can not be achieved, it is necessary to switch to another statin that does not enter into interactions of this type;

- drugs that cause photosensitivity have an additive photosensitizing effect;

- Grapefruit juice increases AUC and Cmof amiodarone by 50% and 84%, respectively;

- fentanyl - risk of bradycardia, lowering blood pressure and cardiac output;

- lidocaine for local local anesthesia and amiodarone Inside - the risk of sinus bradycardia;

- disopyramide, fluoroquinolones, macrolide antibiotics, azoles - the risk of lengthening the interval QT;

- with drugs metabolized with cytochrome P450 AP4: fentanyl, lidocaine, tacrolimus, sildenafil, midazolam, triazolam, ergotamine, statins.

Special instructions:

Before the start of treatment, and every 3 months, it is necessary to carry out ECG monitoring, taking into account that elderly patients have a more pronounced bradycardia, also necessary to conduct a radiological examination of the lungs, evaluate the function of the thyroid gland (the content of hormones), the liver (enzymes).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 the drug Amiodarone-Acry, 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-Acrya 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 treatment with Amiodarone-Acri, 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), transaminases (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 course 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.

Application in pregnancy and lactation is possible only with life-threatening rhythm disturbances with the ineffectiveness of other antiarrhythmic therapy (causes fetal thyroid dysfunction).

After withdrawal, 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 performing surgical procedures, as well as oxygen therapy, it is necessary to warn the doctor about the use of Amiodarone-Acry, as there have been 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 treatment with Amiodarone-Acre, one should refrain from driving motor vehicles and practicing potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 200 mg.

Packaging:

10 tablets per contour cell pack.

2, 3 or 6 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

List B. In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N001750 / 01

Date of registration:18.09.2008 / 30.10.2015

Expiration Date:Unlimited

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp12.08.2017

Illustrated instructions

Instructions

Amiodarone-Acry® (Amiodarone-Akri®)