Amyodaron Belupo - instructions for use, dose, side effects, contraindications

One tablet contains active substance amiodarone hydrochloride 200 mg, and Excipients: corn starch, lactose monohydrate, povidone (K90), magnesium stearate, silicon dioxide colloidal anhydrous, corn pregelatinized starch.

Description:

Round flat white tablets with a fault line on one side.

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; increases the energy reserves of the myocardium (by increasing the content of creatine sulfate, adenosine 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 conversion of T3 to T4 (blockade of thyroxine-5-deo-dodynase) 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 (T3 deficiency can bring to its hyperproduction and thyrotoxicosis). 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 a long oral intake, the mean T1 / 2 is 40 days (this is important in choosing a dose, since it may be necessary for at least 1 month to stabilize the new plasma concentration, while complete elimination may last more than 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 fibrillation 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 blockade

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

- atrioventricular blockade of II - III degree

- 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)

- 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.

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 the drug AMIODARON Belupo 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 large and partly fill the pupil, complaints are possible about the appearance of color halos or fuzziness of the contours), in rare cases, a microcellular retina.

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 level with normal or slightly expressed decrease in T3 (in the absence of clinical signs thyroid dysfunction 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).

From the respiratory system: with prolonged use - cough, dyspnea, alveolar and / or interstitial pneumonia, pulmonary fibrosis, pleurisy, bronchospasm (especially in patients with severe respiratory failure or bronchial asthma).

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; optic neuritis.

From the digestive system: nausea, vomiting, taste disorder, constipation, flatulence, with prolonged use - toxic hepatitis, cholestasis, cirrhosis. Allergic reactions: skin rash, including exfoliative dermatitis.

From the cardiovascular system: sinus bradycardia (refractory to anticholinergics); sinoatrial blockade, AV blockade, with prolonged use - progression of symptoms of heart failure, tachycardia of the type "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, vasculitis.

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 antiarrhythmic agents, MAO inhibitors, pentamidine for parenteral administration, as the risk of developing ventricular tachycardia such as "pirouette" (torsade de pointe).

Uncommon combinations:

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

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

Combinations where caution should be exercised:

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

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

- with cardiac glycosides, tk. there may be violations of automatism (manifested by bradycardia) and atrial-ventricular conduction disorders. 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, cyclosporine, it is possible to increase their concentration in the blood plasma (should monitor the concentration of phenytoin or cyclosporine in the blood plasma);

- colestyramine 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;

- means 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-I, 123-I) and sodium pertechnetate (99mTc) by 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.

- inhibitors of HIV proteases (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) type of 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.

- antiarrhythmics IA class, tricyclic antidepressants, phenothiazines, astemizole, terfenadine, sotalol - risk of arrhythmogenic action (lengthening of the interval QT, polymorphic ventricular tachycardia, predisposition to sinus bradycardia, blockade of the sinus node or AV blockade)

- drugs that cause photosensitivity have an additive photosensitizing effect

- grapefruit juice increases AUC and Cmax of amiodarone by 50% and 84%, respectively

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

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

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

Special instructions:

Before the beginning of treatment, and also every 3 months, it is necessary to carry out ECG monitoring,It should be borne in mind that elderly patients have a more pronounced bradycardia, it is also necessary to perform an X-ray examination of the lungs, to 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 AMIODARON Belupo, ECG changes are possible: lengthening of the interval QT with possible appearance of a prong U. When atrioventricular blockade of II and III degree appears, the sinoatrial blockade, and also

blockade of the legs of the bundle of Hisa, treatment with AMIODARON Beloupol 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 AMIODARON Belupo, 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 an impact on test results

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 the drug AMIODARON Belupo,because 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 treatment with AMIODARON Belugo, one should refrain from driving motor vehicles and practicing potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 200 mg.

Packaging:15 tablets in a blister of PVC film and aluminum foil. For 2 or 4 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

3 years.

Do not use after the expiry date printed on the package!

Terms of leave from pharmacies:On prescription

Registration number:П N014915 / 01

Date of registration:06.05.2008

Expiration Date:Unlimited

The owner of the registration certificate:Beluga, medicines and cosmetics.Beluga, medicines and cosmetics. Croatia

Manufacturer: & nbsp

BELUPO, Pharmaceuticals & Cosmetics, d.d. Croatia

Representation: & nbspBeluga, medicines and cosmetics. Beluga, medicines and cosmetics. Croatia

Information update date: & nbsp12.08.2017

Illustrated instructions

Instructions

Amiodaron Belupo (Amiodarone Belupo)