Cardiodarone - instructions for use, dose, side effects, contraindications

Antiarrhythmic remedy class III. It also has antianginal, coronarodilating, alpha and beta-adrenergic blocking, thyroid-stimulating and hypotensive actions.

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; decreases the heart rate (heart rate); increases energy reserves of the myocardium. Reduces overall peripheral vascular resistance (OPSS) and systemic blood pressure (BP).

Antiarrhythmic effect is due to the effect on the electrophysiological processes of the myocardium; prolongs the action potential of cardiomyocytes, increasing the refractory period of the atria, ventricles, atrioventricular node,a bundle of His and Purkinje fibers, additional ways of carrying out excitation.

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 transformation of T3 in T4), blocks the seizure of these hormones by cardiomyocytes and hepatocytes, which leads to a weakening of the stimulating effect of thyroid hormones on the myocardium (a deficiency of TK can lead to its hyperproduction and thyrotoxicosis).

With intravenous bolus injection, the antiarrhythmic effect of Cardiodarone® is manifested within the first hour after the administration of the drug. With the continuation of parenteral administration (infusion), this effect reaches a maximum within 2 days.

Pharmacokinetics:

After intravenous administration, the maximum concentration of amiodarone is quickly reached in the serum. The subsequent decrease in serum amiodarone concentration is a consequence of the distribution of the substance in the peripheral tissues. The volume of distribution varies from 40 to 130 l / kg. In the muscle of the heart, the maximum concentration after intravenous injection is reached after a few minutes.

Metabolism of amiodarone is carried out mainly in the liver and partly in the intestinal mucosa. In the liver amiodarone is metabolized by cytochrome P450 (isoenzyme CYP3A4). The main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the basic compound.

With intravenous administration, excretion of amiodarone occurs in 2 phases: initial (half-life - 8 minutes), in 2 phase - 4-10 days. The final half-life of desethylamiodarone is 61 days on average. It is excreted with bile (85-95%), the kidneys are excreted less than 1% (therefore, if there is a violation of kidney function, there is no need to change the dosage). Neither amiodarone, nor its metabolites are dialyzed. Amiodarone penetrates the blood-brain barrier and the placenta (10-50%), excreted in breast milk (25% of its dose received by the mother). Connection with blood plasma proteins - 95%.

Indications:

Cardiodarone® in the form of a drug for intravenous administration is used when it is necessary to obtain a rapid therapeutic effect or if therapy is not possible with oral administration in the treatment of severe cardiac arrhythmias, such as life-threatening ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation)supraventricular arrhythmias (usually Wolff-Parkinson-White syndrome, including paroxysm of fibrillation and atrial flutter); atrial and ventricular extrasystole; arrhythmias on the background of coronary or heart failure, parasystole, ventricular arrhythmias in patients with Chagas myocarditis; angina pectoris.

Contraindications:

Hypersensitivity to the drug (including iodine), sinus bradycardia, sinoatrial block, atrioventricular block II and III degree (without using a pacemaker), cardiogenic shock, hypokalemia, collapse, arterial hypotension, sinus node weakness syndrome, heart failure (in decompensation stage), hypothyroidism, hyperthyroidism, interstitial lung diseases, taking MAO inhibitors, pregnancy, lactation, age to 18 years.

Carefully:Chronic heart failure, hepatic insufficiency, bronchial asthma, advanced age (high risk of pronounced bradycardia)

Pregnancy and lactation:

Cardiodarone ® penetrates the placenta into the fetus. It can cause fetal lesions, hypothyroidism and hyperthyroidism in newborns. Therefore, its use during pregnancy is contraindicated.The drug can be administered during pregnancy only if it is clearly necessary (when other antiarrhythmics are ineffective), if the expected result exceeds the risk for the fetus.

Because the amiodarone in significant quantities excreted in breast milk, breastfeeding with the appointment of Cardiodarone® should be discontinued.

Dosing and Administration:

Dosage should always be selected in accordance with the condition of each individual patient.

Intravenous injection

The standard dose is 5 mg / kg of body weight (in patients with heart failure - 2.5 mg / kg) and should be administered for at least 3 minutes. Repeated intravenous injection should not be performed earlier than 15 minutes after the first, because of the possibility of developing irreversible collapse. The therapeutic effect is manifested during the first minutes, and then gradually decreases. In this regard, to maintain a stable effect, intravenous infusion of the drug is necessary.

Intravenous infusion

Initial therapy (loading dose): the usual dose is 5 mg / kg body weight and is injected into 250 ml 5% dextrose (glucose) solution for a period of 20 minutes to 2 hours. The rate of infusion should be selected according to the therapeutic effect.This dose can be repeated 2-3 times within 24 hours. The maximum daily dose should not exceed 1200 mg.

Maintenance dose are 10-20 mg / kg (usually from 600 to 800 mg, but not more than 1200 mg per day). Introduced in 250 ml of a 5% solution of dextrose (glucose). Treatment lasts 4-5 days. If long-term treatment is planned, the first day of the infusion therapy should begin taking tablet forms of Cardiodarone®.

Older patients and children

In the treatment of elderly patients, the lowest loading and maintenance doses of the drug are recommended.

The effectiveness and safety of the use of Cardiodarone ® in children have not been identified.

To dilute Cardiodarone ® solution for intravenous administration, only 5% dextrose solution (glucose) can be used, with the other solutions the drug is not compatible.

Side effects:

The most common side effect in the application of Cardiodarone® in this dosage form is arterial hypotension (10-30%). The occurrence of arterial hypotension and the possibility of developing collapse depend mainly on the speed of infusion, and not on the dose of the drug.Most of these side effects of the drug, due to the short-term use of intravenous injection is of little character.

From the cardiovascular system: sinus bradycardia (refractory to cholinolytics), atrioventricular blockade, with prolonged use - progression of symptoms of heart failure, tachycardia of the type "pirouette", strengthening of the existing arrhythmia or its occurrence, with parenteral use, lowering blood pressure.

From the respiratory system: interstitial pneumonia or alveolitis, pulmonary fibrosis, pleurisy, parenteral use - bronchospasm, apnea (in patients with severe respiratory failure), unproductive cough, shortness of breath.

From the gastrointestinal tract and the hepatobiliary system: nausea, vomiting, constipation, loss of appetite, dullness or loss of taste, abdominal pain, flatulence, rarely transient liver damage (increased activity of "hepatic" enzymes in the blood serum).

With long-term use - toxic hepatitis, cholestasis, jaundice, liver cirrhosis.

Thyroid: during treatment with Cardiodarone® or after its termination, hypothyroidism or hyperthyroidism may occur. In this case, the use of Cardiodarone® should be discontinued. After discontinuing the administration of the drug, the thyroid function after a few months is usually normalized.

From the nervous system: peripheral neuropathy, paresthesia, cerebellar ataxia, headache, neuropathy and / or optic neuritis, polyneuropathy, weakness, dizziness, moderate increase in intracranial pressure, memory impairment, sleep, depression, tremor, extrapyramidal manifestations, ataxia, auditory hallucinations. With parenteral application - craniocerebral hypertension.

From the sense organs: uveitis, the deposition of lipofuscin in the corneal epithelium and visual impairment (blurred vision, limitation of the visual fields - the patient's complaints about luminous points or a veil before the eyes of a bright son), a microcellular retina. More pronounced visual impairment may be a consequence of neuropathy and / or neuritis of the optic nerve. When they appear, the patient should be immediately examined by an ophthalmologist.

From the skin: increased photosensitivity of open body parts (photosensitivity), rash or gray-blue skin coloration may occur during treatment with Cardiodarone® and several weeks after its termination. Rare side effects are skin rash, Stevens-Johnson syndrome, toxic epidermolysis and angioedema. Gray-blue skin color is reversible and usually disappears after discontinuation of the drug.

Laboratory indicators: with long-term use - thrombocytopenia, hemolytic and aplastic anemia, increase in T4 level with a normal or slightly reduced TK level.

Allergic reactions: skin rash, including exfoliative dermatitis.

Other: myopathy, epididymitis, decreased potency, alopecia, vasculitis, fever, sweating.

Local reactions are phlebitis.

Overdose:

When the drug is overdosed, sinus bradycardia, atrioventricular blockade, ventricular tachycardia, polymorphic ventricular tachycardia such as pirouette, liver damage, and lowering of blood pressure are possible.

When an overdose is symptomatic treatment.Bradycardia can be eliminated by atropine, beta-adrenoreceptor agonists, a glucon or a temporary rhythm driver.

Cardiotonics and / or vasoconstrictors are needed to eliminate arterial hypotension. With tachycardia such as "pirouette" - intravenous injection of magnesium salts, pacing. Hemodialysis is not effective.

Interaction:

Co-administration of Cardiodarone® with other anti-arrhythmic drugs (bezpridil, antiarrhythmics IA, III, 1C, sotalol), vincomycin, sultopride, erythromycin (intravenously) and pentamidine (intravenously) is contraindicated due to the possibility of developing polymorphic ventricular tachycardia such as pirouette, lengthening the interval QT, predisposition to sinus bradycardia, blockade of the sinus node or AV blockade.

Tricyclic antidepressants, phenothiazine derivatives, terfenadine and astemizole when combined with Cardiodarone®, the interval is prolonged QT and increase the risk of developing ventricular arrhythmias, especially arrhythmias such as pirouettes.

Cardiodarone® enhances the effect of oral anticoagulants of indirect action - warfarin and acenocoumarol.In these cases, the dose of warfarin should be reduced to 66%, and asenocumarol - to 50% and monitor prothrombin time.

Caution should be exercised if Cardiodarone® is used concomitantly with drugs that can cause hypokalemia: laxatives, stimulants, diuretics that increase potassium excretion, corticosteroids, amphotericin B (intravenously), synthetic corticotropin (tetracosactide). Hypokalemia promotes additional lengthening of the interval QT, which can increase the risk of developing ventricular arrhythmias, including arrhythmias such as pirouettes.

It is not recommended to co-administer Cardiodarone® with blockers of "slow" calcium channels (diltiazem, veralamil, other blockers of "slow" calcium channels) or beta-adrenoblockers, as they increase the risk of bradycardia and oppression of atrioventricular conduction.

When Cardiodarone ® is combined with digoxin, atrioventricular conduction disorders or an increase in serum digoxin concentration (due to a decrease in its excretion) are possible.In such a situation, it is necessary to control the concentration of digoxin in the blood serum, adjust the dose of digoxin (decrease by 1/2) or stop digoxin administration. Simultaneous appointment of "cardiac glycosides" increases the risk of bradycardia and oppression of atrioventricular conduction.

With the simultaneous use of Cardiodarone® with phenytoin (diphenin), clinical signs of a phenytoin overdose may appear due to an increase in serum concentration in the serum. In this case, it is necessary to monitor the concentration of phenytoin and a corresponding decrease in its dose (by 1 / 3-1 / 2).

When the combined use of Cardiodarone ® with cyclosporine, the content of cyclosporine in the serum can increase due to a decrease in the excretion of the drug. In this regard, the dosage of cyclosporine should be adequately scorched.

Cardiodarone® increases the concentration in the blood plasma of quinidine, procainamide, flecainide.

Cardiodarone® can inhibit the absorption by the thyroid gland of sodium iodide (131-1,123-1) and sodium pertechnetate (99mTc).

Kolestyramin reduces absorption, half-life and concentration of amiodarone in the blood plasma, cimetidine - Increases.During general anesthesia, the use of Cardiodarone® requires caution because of the risk of bradycardia (not eliminated by atropine), arterial hypotension, conduction abnormalities, and reduction in stroke volume.

When conducting surgical interventions, notify the anesthesiologist about taking the drug (the possibility of developing acute respiratory distress syndrome in adults immediately after surgery).

Preparations that cause photosensitivity have an additive photosensitizing effect.

Special instructions:

Parenteral administration of the drug is carried out only in a hospital under the control of blood pressure, heart rate and ECG.

Before the start of therapy, it is necessary to perform an X-ray examination of the lungs, evaluate the function of the thyroid gland (the concentration of hormones), the liver (transaminase activity) and the content of plasma electrolytes. During the treatment periodically carry out the analysis of transaminases (with a threefold increase or a doubling in the case of initially increased their activity dose is reduced until the complete cessation of therapy).It is necessary to periodically observe the oculist (revealing significant deposits in the cornea, or the development of visual impairment requires the drug to be discontinued).

Intravenous injection (bolus administration) is usually not recommended because of possible hemodynamic disorders (pronounced decrease in blood pressure, circulatory insufficiency). They can be carried out only in emergency cases, when other therapy is ineffective.

If possible, Cardiodarone® solution should be administered as an intravenous infusion. During the infusion therapy, arterial hypotension, bradycardia and atrioventricular blockade may occur. In this regard, the speed of infusion should be carefully monitored. Since intravenous infusions of Cardiodarone® can be accompanied by phlebitis, the drug should be administered through a central venous catheter.

Progressing dyspnea and non-productive cough may be signs of a toxic effect of the drug on the lungs.

Patients treated with Cardiodarone® may develop acute respiratory distress syndrome after surgery, after careful surgery, patients must be carefully monitored,monitoring of oxygen concentration in the inspired air (FiO2) and indices of tissue oxygenation (SaO2, PaO2).

Laboratory Tests

Cardiodarone® contains iodine and therefore can change the results of tests of accumulation of radioactive iodine in the thyroid gland (change in the concentration of T3, T4, TTG).

Form release / dosage:

Solution for intravenous administration 50 mg / ml.

Packaging:3 ml in neutral glass ampoules. 5 or 10 ampoules with instructions for use and a knife for opening ampoules or a scarifier ampullum in a pack or box of cardboard; or 5 or 10 ampoules per contour cell pack of a polyvinyl chloride film. For 1 or 2 contour packs with instructions for use and a knife for opening ampoules or a scarifier ampullum in a pack of cardboard. When you pack the ampoules with a break ring or break point, the ampoule opener or ampoule scapper is not put in.

Storage conditions:

In the dark place at a temperature of 15 ° C to 25 ° C.

Keep out of the reach of children.

Shelf life:

1 year. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N000737 / 01

Date of registration:23.12.2011

Expiration Date:Unlimited

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

NOVOSIBHIMFARM, OJSC Russia

Information update date: & nbsp10.12.2017

Illustrated instructions

Instructions

Cardiodarone® (Cardiodarone®)