2010/09/20

Amiodarone Belupo

Composition, structure and packing

Tablets are white, round, flat, with a fault line on one side.

1 tab.

Amiodarone Hydrochloride 200 mg.

Excipients: corn starch, lactose monohydrate, povidone K90, magnesium stearate, colloidal silicon dioxide (anhydrous), starch pregelatinized corn.

Pharmacological action

Antiarrhythmics, class III, has antianginal action. Antiarrhythmic effect on the ability to increase the duration of the action potential of cardiomyocytes and effective refractory period of atria, ventricles, AV node, bundle of His, Purkinje fibers. This is accompanied by a decrease in automaticity of sinus node slowing AV-conduction, reduced excitability of cardiomyocytes. It is believed that the mechanism of increasing the duration of the action potential associated with the blockade of potassium channels (decreased excretion of potassium ions from the cardiomyocytes). By blocking the inactivated "fast" sodium channels, has effects that are characteristic for class I antiarrhythmics. Hinders slow (diastolic) depolarization of the cell membranes of sinus node, causing bradycardia, depresses AV conducting (the effect of antiarrhythmic drugs of Class IV).

Antianginal effect is due koronarorasshiryayuschim and antiadrenergicheskim effect, decreasing myocardial oxygen demand. Has an inhibiting effect on the α-and β-adrenergic receptors of the cardiovascular system (without their complete blockade). Decreases sensitivity to hyperstimulation of the sympathetic nervous system tone of the coronary vessels, increase coronary blood flow, slows heart rate, increases myocardial energy reserves (by increasing the content kreatinsulfata, adenosine and glycogen). Reduces total peripheral vascular resistance and systemic blood pressure (with a / in the introduction).

It is thought that amiodarone may increase the level of phospholipids in tissues.

Contains iodine. Affects metabolism of thyroid hormones, inhibits the conversion of T3 to T4 (thyroxine blockade-5-deyodinazy) 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 can lead to overproduction and hyperthyroidism) .

If ingestion onset of action - from 2-3 days to 2-3 months, the duration of action also Variable - from several weeks to several months.

Following in / introduction of the maximum effect is achieved through a 1-30 minutes and lasts 1-3 hours

Pharmacokinetics

Once inside slowly absorbed from the gastrointestinal tract, absorption is 20-55%. Cmax plasma levels achieved after 3-7 hours

As a result of intensive accumulation in adipose tissue and organs with high perfusion (liver, lungs, spleen) has a large and variable Vd and is characterized by a slow attainment of equilibrium and therapeutic concentrations in blood plasma and for long-term excretion. Amiodarone is determined in the blood plasma up to 9 months after the cessation of its use. Protein binding is high - 96% (62% - with albumin, 33.5% - with β-lipoproteins) ..

It penetrates through the BBB and placental barrier (10-50%) is excreted in breast milk (25% of the dose received by the mother).

Intensively metabolized in the liver with the formation of the active metabolite desetilamiodarona, as well as, apparently, by deyodirovaniya. In long-term treatment of iodine concentration can reach 60-80% concentration of amiodarone. Is an inhibitor of isoenzymes CYP2C9, CYP2D6 and CYP3A4, CYP3A5, CYP3A7 in the liver.

Withdrawal is biphasic. Once inside T1 / 2 in the initial phase of 4-21 days, in the terminal phase - 25-110 days; desetilamiodarona - an average of 61 days. Typically, at course oral application T1 / 2 of amiodarone is 14-59 days. After i / v administration of amiodarone T1 / 2 in the terminal phase is 4-10 days.

Derive mainly from the bile through the intestines, there may be a little enterohepatic recycling. In very small amounts of amiodarone and desetilamiodaron excreted in urine.

Amiodarone and its metabolites are not displayed during dialysis.

Statement
treatment and prevention of paroxysmal arrhythmias: the life-threatening ventricular arrhythmias (including ventricular tachycardia),
prevention of ventricular fibrillation (also after cardioversion)
supraventricular arrhythmias (usually with inefficiency or inability to another therapy, especially those associated with the syndrome, WPW), including paroxysm of fibrillation and atrial flutter;
atrial and ventricular premature beats;
fibrillation on a background of coronary insufficiency or congestive heart failure,
parasystole,
ventricular arrhythmias in patients with Chagas myocarditis;
angina.

Dosage regimen

When administered to adult initial single dose of 200 mg. For children the dose is 2.5-10 mg / day. Scheme and the duration of treatment set individually.

For iv injection (jet or drip) single dose of 5 mg / kg daily dose - up to 1.2 g (15 mg / kg).

Side effect

Since the cardiovascular system: sinus bradycardia (refractory to M-holinoblokatoram), AV block, long-term use - the progression of chronic heart failure, ventricular Artime type "pirouette", strengthening of existing arrhythmias or her appearance, with parenteral use - lowering blood pressure.

On the part of the endocrine system: the development of hypo-or hyperthyroidism.

On the part of the respiratory system: long-term use - cough, dyspnea, interstitial pneumonitis or alveolitis, fibrosis of the lungs, pleurisy, with parenteral use - bronchospasm, apnea (in patients with severe respiratory failure).

On the part of the digestive system: nausea, vomiting, loss of appetite, dullness or loss of taste, feeling of heaviness in the epigastric, abdominal pain, constipation, flatulence, diarrhea, rarely - increased activity of hepatic transaminases, with prolonged use - toxic hepatitis, cholestasis, jaundice , cirrhosis of the liver.

From the side of the central nervous system and peripheral nervous system: headache, weakness, dizziness, depression, fatigue, paresthesia, auditory hallucinations, with prolonged use - peripheral neuropathy, tremors, memory impairment, sleep, extrapyramidal signs, ataxia, optic neuritis, with parenteral application - intracranial hypertension.

From the senses: uveitis, deposition of lipofuscin in the corneal epithelium (if the deposits are large and partially fill the pupil - a complaint at the luminous point, or the veil before the eyes in bright light), mikrootsloyka retina.

The part of the hemopoietic system: thrombocytopenia, hemolytic and aplastic anemia.

Dermatological reactions: skin rash, exfoliative dermatitis, photosensitivity, alopecia, rarely - gray-blue color of the skin.

Local reactions: thrombophlebitis.

Other: epididymitis, myopathy, reduced potency, vasculitis, with parenteral use - a fever, increased sweating.

Contraindications
sinus bradycardia,
SSS,
sinoatrial block,
AV block II-III degree (without pacemaker)
cardiogenic shock,
hypokalemia, collapse,
hypotension,
hypothyroidism,
thyrotoxicosis,
interstitial lung disease
receiving MAO inhibitors, pregnancy,
lactation,
Hypersensitivity to amiodarone and iodine.

Pregnancy and lactation

Do not use this during pregnancy and lactation.

Amiodarone and desmetilamiodaron penetrate through the placental barrier, its concentration in the blood of the fetus, are respectively 10% and 25% of the concentration in maternal blood.

Amiodarone and desmetilamiodaron stand with breast milk.

Cautions

C use caution in patients with chronic heart failure, liver failure, asthma, elderly patients (high risk of severe bradycardia) in 18 years of age (efficacy and safety have not been established).

It should not be administered to patients with severe respiratory failure.

Before the use of amiodarone should be x-ray of the lungs and thyroid function, if necessary, to the correction of electrolyte disturbances.

With long-term treatment requires regular monitoring of thyroid function, consult an ophthalmologist and X-ray examination of the lungs.

Parenteral may be used only in specialized departments of hospitals under the constant control of blood pressure, heart rate and ECG.

Patients receiving amiodarone should avoid direct exposure to sunlight.

If you cancel amiodarone possible recurrence of cardiac arrhythmias.

May influence the test results of accumulation of radioactive iodine in the thyroid gland.

Should not be used concurrently with amiodarone chinidin, beta-blockers, calcium channel blockers, digoxin, coumarins, doksepinom.

Drug Interactions

Drug Interactions of amiodarone with other drugs may be even a few months after the end of its application due to the long half-life.

With simultaneous use of amiodarone and antiarrhythmics class IA (including dizopiramid) increases the QT interval due to the additive effect on its value and increases the risk of ventricular tachycardia type "pirouette".

With simultaneous use of amiodarone with laxatives, which can cause hypokalemia, increased risk of ventricular arrhythmias.

Means causing hypokalemia, including diuretics, corticosteroids, amphotericin B (IV), tetrakozaktid with simultaneous application with amiodarone caused an increase in QT interval and increased risk of ventricular arrhythmias (including type "pirouette").

With simultaneous use of funds for general anesthesia, oxygen therapy is a risk of bradycardia, hypotension, conduction disturbances, reducing the stroke volume of the heart, which apparently is due to additive cardiodepressive and vasodilating effects.

With simultaneous use of tricyclic antidepressants, phenothiazines, astemizol, terfenadin cause an increase in QT interval and increased risk of ventricular arrhythmias, especially type "pirouette".

With the simultaneous use of warfarin, fenprokumona, atsenokumarola increased anticoagulant activity and increased risk of bleeding.

With simultaneous application vinkamina, sultoprida, erythromycin (IV), pentamidine (IV, V / m) increases the risk of ventricular arrhythmias such as "pirouette".

With the simultaneous use may increase the concentration of dextromethorphan in plasma due to the reduction rate of its metabolism in the liver, which is caused by inhibition of CYP2D6 isoenzyme of cytochrome P450 under the influence of amiodarone and slower elimination of dextromethorphan from the body.

With simultaneous use of digoxin significantly increased the concentration of digoxin in plasma by reducing its clearance and, therefore, increases the risk of digitalis intoxication.

With simultaneous application of diltiazem, verapamil increased the negative inotropic effect, bradycardia, conduction disturbances, AV-block.

A case of increasing concentrations of amiodarone in blood plasma in its simultaneous application with indinavir. It is believed that ritonavir, nelfinavir, saquinavir will provide a similar effect.

With simultaneous application of decreasing concentrations kolestiramina amiodarone in blood plasma because of its binding to kolestiraminom and reduce the absorption from the gastrointestinal tract.

There are reports of increased concentration of lidocaine in blood plasma, while the use of amiodarone and the development of convulsions, apparently due to inhibition of metabolism of lidocaine under the influence of amiodarone.

It is believed that the possible synergies with respect to suppress the sinus node.

With simultaneous application of lithium carbonate may develop hypothyroidism.

With simultaneous application of procainamide increased the QT interval due to the additive effect on its value and risk of ventricular tachycardia type "pirouette". Higher concentrations in blood plasma procainamide and its metabolite N-atsetilprokainamida and increased side effects.

With simultaneous application of propranolol, metoprolol, sotalol may be hypotension, bradycardia, ventricular fibrillation, asystole.

With simultaneous application trazodona described the case of arrhythmia type "pirouette".

With simultaneous application of quinidine increases the QT interval due to the additive effect on its value and risk of ventricular tachycardia type "pirouette". Increasing concentrations of quinidine in blood plasma and increasing its side effects.

With simultaneous application described a case gain side effects of clonazepam, which is apparently due to its cumulation due to inhibition of oxidative metabolism in the liver under the influence of amiodarone.

With simultaneous application tsizaprida significantly increased the QT interval due to the additive action, the risk of ventricular arrhythmias (including type "pirouette").

With simultaneous application of increasing the concentration of cyclosporine in the blood plasma, the risk of nephrotoxicity.

A case of pulmonary toxicity when used with cyclophosphamide in high doses and amiodarone.

Increasing the concentration of amiodarone in blood plasma as a result of slowing down its metabolism under the influence of cimetidine and other inhibitors of microsomal liver enzymes.

It is believed that due to the inhibition under the influence of amiodarone in liver enzymes, with the participation of which is the metabolism of phenytoin, may increase the concentration of the latter in the blood plasma and increasing its side effects.

As a consequence of induction of microsomal liver enzymes influenced the rate of metabolism of phenytoin increased amiodarone in the liver and decreases its concentration in blood plasma.