Amiodarone - instructions for use, doses, side effects, contraindications

Active substance: Amiodarone hydrochloride in terms of 100% 200,00 mg; Excipients: lactose monohydrate - 160.00 mg; Povidone K-17 - 4,00 mg; calcium stearate - 2.00 mg; potato starch - up to 400,00 mg.

Description:

Tablets of white or almost white color, flat-cylindrical, with a risk and a facet.

Pharmacotherapeutic group:Antiarrhythmic drug

ATX: & nbsp

C.01.B.D.01 Amiodarone

Pharmacodynamics:

Amiodarone belongs to the third class of antiarrhythmic drugs (repolarization inhibitor class) and has a unique mechanism of antiarrhythmic action, in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (blockade of sodium channels), class IV antiarrhythmics (calcium channel blockade ) and non-competitive beta-adrenergic blocking action.

In addition to antiarrhythmic action, he has antianginal, coronary dilatory, alpha and beta adrenoblocking effects.

Antiarrhythmic properties:

- increase in the duration of the third phase of the action potential of cardiomyocytes, mainly due to blocking of the ion current in potassium channels (the effect of class III antiarrhythmics according to Williams classification);

- a decrease in the automatism of the sinus node, which leads to a decrease in the heart rate;

- non-competitive blockade of alpha- and beta-adrenergic receptors;

- slowing of sinoatrial, atrial and atrioventricular conduction, more pronounced with tachycardia;

- no changes in ventricular conduction;

- an increase in refractory periods and a decrease in the excitability of the myocardium of the atria and ventricles, as well as an increase in the refractory period of the atrioventricular node;

- slowing the conduction and prolongation of the refractory period in additional beams of the atrioventricular conduction.

Other effects:

- absence of negative inotropic effect when taken orally;

- decrease in oxygen consumption by myocardium due to a moderate decrease in peripheral resistance and heart rate;

- increase in coronary blood flow due to direct effect on the smooth muscles of the coronary arteries;

- maintaining cardiac output by reducing the pressure in the aorta and reducing peripheral resistance;

- influence on the exchange of thyroid hormones: inhibition of transformation T₃ in T₄ (blockade of thyroxine-5-deiodinase) and blocking the seizure of these hormones by cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium.Therapeutic effects are observed on average a week after the start of the drug (from several days to two weeks). After the termination of its reception amiodarone is determined in the blood plasma for 9 months. It should be taken into account the possibility of maintaining the pharmacodynamic action of amiodarone within 10-30 days after its withdrawal.

Pharmacokinetics:

Bioavailability after ingestion varies from 30 to 80% in different patients (mean value about 50%). After a single intake of amiodarone, the maximum concentrations in the blood plasma are reached after 3-7 hours. However, the therapeutic effect usually develops a week after the start of the drug (from several days to two weeks). Amiodarone is a drug with a slow intake of tissue and high affinity for them. The connection with plasma proteins is 95% (62% with albumin, 33.5% with beta-lipoproteins). Amiodarone has a large volume of distribution. During the first days of treatment, the drug accumulates in almost all tissues, especially in adipose tissue and in addition to it in the liver, lungs, spleen and cornea. Amiodarone metabolized in the liver using isoenzymes CYP3A4 and CYP2C8. Its main metabolite, desethylamiodarone, is pharmacologically active and can enhance the antiarrhythmic effect of the basic compound. Amiodarone and its active metabolite desethylamiodarone in vitro have the ability to inhibit isoenzymes CYP1A1, CYP1A2, CYP2C19, CYP2D6, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and desethylamiodarone also demonstrated the ability to inhibit certain transporters, such as P-glycoprotein (P-gp) and carrier of organic cations (PKK2). In vivo interaction of amiodarone with substrates of isozymes CYP3A4, CYP2C9, CYP2D6 and P-gp.

The removal of amiodarone begins in a few days, and the achievement of a balance between the admission and withdrawal of the drug (the achievement of the equilibrium state) occurs after one to several months, depending on the individual characteristics of the patient. The main way to remove amiodarone is the intestine. Amiodarone and its metabolites are not excreted by hemodialysis. Amiodarone has a long half-life with a large individual variability (therefore, when choosing a dose, for example, increasing or decreasing it, it should be remembered that at least 1 month is needed to stabilize the new plasma concentration of amiodarone).Excretion ingestion takes place in two phases: initial half-life (the first phase) - 4-21 hour half-life in the 2nd phase - 25-110 days. After continued oral administration, the average half-life is 40 days. After the withdrawal of the drug, the complete removal of amiodarone from the body can continue for several months. Each dose of amiodarone (200 mg) contains 75 mg of iodine. Part of the iodine released from the drug found in the urine and in the form of iodide (6 mg per 24 hours at a daily dose of 200 mg amiodarone). Most iodine remaining in a preparation is outputted through the intestine after passing through the liver, but long-term treatment with amiodarone concentration of iodine may reach 60-80% of amiodarone concentration in the blood. The features explained pharmacokinetics application "Stress" doses, which is aimed at rapid achievement of the desired level of impregnation of fabrics in which manifests its therapeutic effect.

Pharmacokinetics in renal failure

In connection with minor renal excretion of the drug in patients with renal insufficiency is not required amiodarone dose adjustment.

Indications:

Relapse prevention

Life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be initiated in a hospital with careful cardiac monitoring).
Supraclavicular paroxysmal tachycardias:
- documented attacks of recurrent persistent supraventricular paroxysmal tachycardia in patients with organic heart diseases;
- documented attacks of recurrent persistent supraventricular paroxysmal tachycardia in patients without organic heart disease, when antiarrhythmic drugs of other classes are not effective or there are contraindications to their use;
- documented attacks of recurrent persistent supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome.
Atrial fibrillation (atrial fibrillation) and atrial flutter.

Preventing sudden arrhythmic death in high-risk patients

Patients after a recent myocardial infarction with more than 10 ventricular extrasystoles per hour, clinical manifestations of chronic heart failure, and a reduced fraction of left ventricular ejection (less than 40%).

Amiodarone can be used in the treatment of rhythm disturbances in patients with coronary heart disease and / or impaired left ventricular function.

Contraindications:

Hypersensitivity to iodine, amiodarone or excipients of the drug.
Lactose intolerance (lactase deficiency), glucose-galactose malabsorption syndrome (the drug contains lactose).
Syndrome of weakness of the sinus node (sinus bradycardia, sinoatrial block), except for cases of their correction by an artificial pacemaker (danger of "stopping" the sinus node).
Atrioventricular blockade of II-III degree, in the absence of an artificial pacemaker (pacemaker).
Hypokalemia, hypomagnesemia.
Combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including ventricular "pirouette" tachycardia (see section "Interaction with other drugs"):
- antiarrhythmics: IА class (quinidine, hydroquinidine, disopyramide, procainamide);
- Class III antiarrhythmic drugs (dofetilide, ibutilide, brethil tosylate); sotalol;
- other (not anti-arrhythmic) drugs, such as beprideal; wincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; cisapride; tricyclic antidepressants; macrolide antibiotics (in particular erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine; astemizole, terfenadine; fluoroquinolones.
Congenital or acquired elongation of the QT interval.
Thyroid dysfunction (hypothyroidism, hyperthyroidism).
Interstitial lung disease.
Pregnancy (see "Application during pregnancy and during lactation").
Lactation period (see "Application during pregnancy and during lactation").
Age to 18 years (effectiveness and safety not established).

Carefully:In case of decompensated or severe chronic (III-IV functional class according to the NYHA classification) of heart failure, hepatic insufficiency, bronchial asthma,severe respiratory failure, in elderly patients (high risk of severe bradycardia), with atrioventricular blockade of the I degree.

Pregnancy and lactation:

Pregnancy

Currently available clinical information is not sufficient to determine whether embryos can develop or develop in the first trimester of pregnancy.

Since the fetal thyroid begins to bind iodine only from the 14th week of pregnancy (amenorrhea), then it is not expected that amiodarone will affect it if it is used earlier. Excess iodine in the use of the drug after this period can lead to the appearance of laboratory symptoms of hypothyroidism in a newborn or even to the formation of a clinically significant goiter in it. Due to the effect of the drug on the thyroid gland of the fetus, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit exceeds the risks (with life-threatening ventricular arrhythmias).

Breastfeeding period

Amiodarone is excreted in breast milk in significant amounts, so it is contraindicated in the period of breastfeeding.If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The drug should be taken only as directed by a doctor! Amiodarone tablets are taken orally, before meals and washed down with a sufficient amount of water.

Load ("saturating") dose

Various saturation schemes can be used.

In the hospital the initial dose divided into several doses ranges from 600-800 mg (to a maximum of 1200 mg) per day until a total dose of 10 g is reached (usually within 5-8 days).

Ambulatory the initial dose divided into several doses ranges from 600 to 800 mg per day until a total dose of 10 g is reached (usually within 10-14 days).

Maintenance dose can vary in different patients from 100 to 400 mg / day. A minimum effective dose should be applied in accordance with the individual therapeutic effect.

As Amiodarone has a very long half-life, it can be taken every other day or take breaks in its reception 2 days a week.

The average therapeutic single dose 200 mg.

The average therapeutic daily dose 400 mg.

Maximum single dose 400 mg.

The maximum daily dose - 1200 mg.

Side effects:

The frequency of side effects is given in accordance with the classification of the World Health Organization: very often - not less than 10%; often - not less than 1 and less than 10%; infrequently - not less than 0.1% and less than 1%; rarely - not less than 0.01% and less than 0.1%; very rarely - less than 0.01%, including isolated cases; the frequency is unknown - according to the available data, the frequency can not be determined.

From the heart

Often - bradycardia, usually mild, the severity of which depends on the dose of the drug;

Infrequently - conduction disorders (sinoatrial block, atrioventricular blockade of various degrees), arrhythmogenic action (there are reports of new arrhythmias, or exacerbation of existing arrhythmias, in some cases - with subsequent cardiac arrest).

In the light of available data, it is impossible to determine whether this is caused by the use of the drug, or is associated with the severity of the cardiovascular pathology, or is a consequence of ineffective treatment. These effects are observed mainly in cases of drug use Amiodarone together with drugs that prolong the period of repolarization of the ventricles of the heart (QT intervalc) or in violation of the water-electrolyte balance (see the section "Interaction with other medicinal products").

Rarely - marked bradycardia or, in exceptional cases, stopping the sinus node, which were noted in some patients (patients with sinus node dysfunction and elderly patients).

Frequency unknown - progression of chronic heart failure (with prolonged use); ventricular "pirouette" tachycardia (see the sections "Interaction with other medicinal products", subsection "Pharmacodynamic interaction" and "Special instructions").

From the digestive system

Often - nausea, vomiting, dysgeusia (dullness or loss of taste sensations), usually occurring when taking a loading dose and passing after a dose reduction.

From the liver and biliary tract

Often - an isolated increase in the activity of transaminases in the blood serum, usually moderate (1.5 to 3 times the normal values), observed at the beginning of the treatment and decreasing with a decrease in dose, or even spontaneously.

Often - acute liver damage with increased transaminase activity and / or jaundice, including the development of hepatic insufficiency, sometimes fatal (see section "Special instructions").

Rarely - chronic liver disease (pseudo-alcoholic hepatitis, cirrhosis) is sometimes fatal. Even with a moderate increase in transaminase activity in the blood after treatment lasting more than 6 months, chronic liver damage should be suspected.

From the respiratory system, organs of the chest and mediastinum

Often - pulmonary toxicity, sometimes fatal (alveolar / interstitial pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans with pneumonia). Although these changes may lead to the development of pulmonary fibrosis, they are generally reversible in the early cancellation of amiodarone, either with or without glucocorticosteroids. Clinical manifestations usually disappear within 3-4 weeks. Restoration of the radiographic picture and function of the lungs takes place more slowly (in a few months). Appearance in the patient receiving amiodarone, pronounced dyspnea or dry cough, as accompanied,and not accompanied by deterioration of the general condition (increased fatigue, lower body weight, increased body temperature) requires chest radiography and, if necessary, drug withdrawal.

Rarely - bronchospasm in patients with severe respiratory failure, especially in patients with bronchial asthma; acute adult respiratory distress syndrome, sometimes fatal and usually developing immediately after surgical interventions (it is assumed that it is possible to interact with a high concentration of oxygen) (see section "Special instructions").

Frequency unknown - Pulmonary bleeding.

Disturbances on the part of the organ of sight

Often - microdeposition in the epithelium of the cornea, consisting of complex lipids, including lipofuscin, they are usually limited to the area of the pupil and do not require discontinuation of treatment and disappear after the drug is discontinued. Sometimes they can cause visual disturbances in the form of a color halo or fuzziness of contours under bright light.

Rarely - Several cases of optic neuritis / visual neuropathy have been described.Their relationship with the administration of amiodarone has not been established to date. However, because optic neuritis can lead to blindness, with the appearance of blurred vision or reduced visual acuity against the background of taking the drug Amiodarone, it is recommended to conduct a full ophthalmological examination, including fundoscopy, and in case of optic neuritis, stop taking amiodarone.

Disorders from the endocrine system

Often - hypothyroidism with its classical manifestations: weight gain, chilliness, apathy, decreased activity, drowsiness, excessive bradycardia compared with the expected effect of amiodarone (The diagnosis is confirmed by the detection of an elevated serum thyrotropic hormone (TSH) concentration (using a supersensitive TSH assay) Thyroid function normalization is usually observed within 1-3 months after discontinuation of treatment .In situations involving a life-threatening condition, amiodarone treatment may be continued, with simultaneous additional use of L-thyroxin under the control of serum TSH concentration.); hyperthyroidism, sometimes fatal, the appearance of which is possible during and after treatment (cases of hyperthyroidism that developed several months after the abolition of amiodarone have been described). Hyperthyroidism proceeds more secretively with a small number of symptoms: a slight unexplained weight loss, a decrease in antiarrhythmic and / or antianginal efficacy; mental disorders in elderly patients or even the phenomenon of thyrotoxicosis. The diagnosis is confirmed by the detection of a reduced concentration of serum TSH (determination with the help of hypersensitivity analysis of TSH). When revealing hyperthyroidism amiodarone should be canceled. Normalization of thyroid function usually occurs within a few months after drug withdrawal. In this case, clinical symptoms are normalized earlier (3-4 weeks) than normalization of the concentration of thyroid hormones. Severe cases can lead to death, so in such cases, urgent medical intervention is required. Treatment in each case is selected individually.If the patient's condition worsens, both because of thyrotoxicosis itself and due to the dangerous imbalance between the oxygen demand for myocardium and its delivery, it is recommended that treatment be started immediately: the use of antithyroid drugs (which may not always be effective in this case), treatment with glucocorticosteroids (1 mg / kg), which lasts long enough (3 months), the use of beta-blockers.

Rarely - syndrome of impaired secretion of antidiuretic hormone.

From the skin and subcutaneous tissues

Often - photosensitization.

Often - in the case of prolonged use of the drug in high daily doses, grayish or bluish skin pigmentation may be observed; after the cessation of treatment, this pigmentation slowly disappears.

Rarely - during the radiation therapy may occur cases of erythema; skin rash, usually mildly specific, exfoliative dermatitis; alopecia.

Frequency unknown - hives.

From the nervous system

Often - tremor or other extrapyramidal symptoms; sleep disturbances, including nightmares.

Infrequently - sensorimotor peripheral neuropathies and / or myopathy, usually reversible within a few months after drug withdrawal, but sometimes not completely.

Rarely - cerebellar ataxia, benign intracranial hypertension (pseudotumor of the brain), headache.

From the side of the vessels

Rarely - Vasculitis.

From the genitals and breast

Rarely - epididymitis, impotence.

On the part of the blood and lymphatic system

Rarely - hemolytic anemia, aplastic anemia, thrombocytopenia.

From the immune system

Frequency unknown - angioedema (edema of Quincke).

Laboratory and instrumental data

Rarely - Increased serum creatinine concentration. General disorders

Frequency unknown - formation of granulomas, including bone marrow granuloma.

Overdose:

When ingesting very large doses, several cases of sinus bradycardia, cardiac arrest, attacks of ventricular tachycardia, paroxysmal ventricular "pirouette" tachycardia, and liver damage are described. It is possible to slow the atrioventricular conduction, to strengthen the already existing heart failure.

Treatment should be symptomatic (gastric lavage, the use of activated charcoal (if the drug is taken recently), in the remaining cases, symptomatic therapy is performed: with bradycardia, beta-adrenostimulyatory or installation of a pacemaker, with ventricular "pirouette" tachycardia - intravenous injection of magnesium salts or pacing.

Neither amiodarone, nor its metabolites are removed during hemodialysis. There is no specific antidote.

Interaction:

Pharmacodynamic interaction

Medications that can cause a bidirectional ventricular "pirouette" tachycardia or increase duration of QT interval

Medications that can cause ventricular "pirouette" tachycardia

Combination therapy with drugs that can cause the ventricular "pirouette" tachycardia is contraindicated, as the risk of developing a potentially lethal ventricular "pirouette" tachycardia increases.

- Antiarrhythmic drugs: IА class (quinidine, hydroquinidine, disopyramide, procainamide), sotalol, beprideal.

- Other (non-antiarrhythmic) medications, such as: wincamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin with intravenous administration, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine; astemizole; terfenadine.

Drugs that can increase the duration of the QT interval

Joint use of amiodarone with drugs that can increase the duration of the QT interval should be based on a careful assessment for each patient of the relationship between expected benefit and potential risk (the possibility of an increased risk of ventricular "pirouette" tachycardia) (see section "Special instructions"), Such combinations must be constantly monitored by ECG patients (for eliciting the prolongation of the QT interval), the content of potassium and magnesium in the blood.

In patients receiving amiodarone, fluoroquinolones should be avoided, including moxifloxacin.

Medicinal products that reduce the heart rate (heart rate) or cause a violation of automatism or conduction

Combination therapy with these drugs is not recommended. Beta-adrenoblockers, blockers of "slow" calcium channels, decreasing heart rate (verapamil, diltiazem), can cause violations of automatism (the development of excessive bradycardia) and conduction.

Medications that can cause hypokalemia

Unsupported combinations

With laxatives, stimulating intestinal motility, which can cause hypokalemia, which increases the risk of developing ventricular "pirouette" tachycardia. When combined with amiodarone, laxatives of other groups should be used.

Combinations requiring caution when used:

- with diuretics, causing hypokalemia (in monotherapy or in combination with other drugs);

- with systemic corticosteroids (glucocorticosteroids, mineralocorticosteroids), tetracazactide;

- with amphotericin B (intravenous administration).

It is necessary to prevent the development of hypokalemia, and in case of its occurrence to restore to normal levels of potassium in the blood, control the content of electrolytes in the blood and ECG (for possible extension QT interval), and in case of ventricular "the twisting 'tachycardia should not be used antiarrhythmic drugs (ventricular pacing, intravenous administration of magnesium salts should be started).

Medicinal preparations for inhalation anesthesia

The possibility of developing the following serious complications in patients taking amiodarone, when they receive general anesthesia: bradycardia (resistant to atropine), arterial hypotension, conduction disorders, reduction in cardiac output.

There were very rare cases of serious complications from the respiratory system, sometimes fatal (acute adult respiratory distress syndrome) which developed immediately after surgery, the occurrence of which is associated with high oxygen concentrations.

Medications that reduce heart rate (clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine bromide, neostigmine bromide), pilocarpine)

The risk of developing excessive bradycardia (cumulative effects).

Influence of amiodarone on other drugs

Amiodarone and / or its metabolite, desethylamiodarone, inhibit the isoenzymes CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-gp and can increase the systemic exposure of drugs that are their substrates. Due to the prolonged half-life of amiodarone, this interaction can be observed even a few months after discontinuation of its administration.

Drugs that are substrates of P-gp

Amiodarone is an inhibitor of P-gp. It is expected that its joint administration with drugs that are substrates of P-gp, will lead to an increase in systemic exposure of the latter.

Cardiac glycosides (medicines of digitalis)

The possibility of violations of automatism (pronounced bradycardia) and atrial-ventricular conduction.In addition, with the combination of digoxin with amiodarone, an increase in the concentration of digoxin in the blood plasma is possible (due to a decrease in its clearance). Therefore, when digoxin is combined with amiodarone, it is necessary to determine the concentration of digoxin in the blood and to monitor possible clinical and electrocardiographic manifestations of digitalis intoxication. You may need to reduce the dosage of digoxin.

Dabigatran

Caution should be exercised when using amiodarone with dabigatran at the same time because of the risk of bleeding. Dabigatran dose may need to be adjusted in accordance with the instructions in its instructions for use.

Drugs that are substrates of the isoenzyme CYP2S9

Amiodarone increases the concentration in the blood of drugs that are substrates of the isoenzyme CYP2C9, such as warfarin or phenytoin by inhibiting cytochrome P450 2C9.

Warfarin

When warfarin is combined with amiodarone, the effects of an indirect anticoagulant may increase, which increases the risk of bleeding. It should be more often monitored prothrombin time (by determining the International Normalized Ratio) and corrected for doses of indirect anticoagulants, as during treatment with amiodarone,and after the termination of its reception.

Phenytoin

When phenytoin is combined with amiodarone, an overdose of phenytoin may develop, which may lead to the appearance of neurologic symptoms; requires clinical monitoring and, at the first signs of an overdose, a decrease in the dose of phenytoin, it is desirable to determine the concentration of phenytoin in the blood plasma.

Drugs that are the substrates of the isoenzyme CYP206

Flecainide

Amiodarone increases the plasma concentration of flecainide by inhibiting the isoenzyme CYP2D6. In this connection correction of doses of flecainide is required.

Drugs that are substrates of the isoenzyme CYP3A4

When combined with amiodarone, the inhibitor of the isoenzyme CYP3A4, these preparations can increase their plasma concentrations, which can lead to an increase in their toxicity and / or increase pharmacodynamic effects and may require a reduction in their doses. Below are listed such preparations.

Cyclosporin

The combination of cyclosporine with amiodarone may increase the concentration of cyclosporine in the blood plasma, a dose adjustment is necessary.

Fentanyl

The combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of developing its toxic effects.

Inhibitors of HMG-CoA reductase (statins) (simvastatin, atorvastatin and lovastatin)

Increased risk of muscular toxicity of statins when administered concomitantly with amiodarone. the use of statins not metabolized by the CYP3A4 isoenzyme is recommended.

Other drugs metabolized by the isoenzyme CYP3A4: lidocaine (risk of developing sinus bradycardia and neurologic symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (the risk of increasing its side effects), midazolam (risk of development of psychomotor effects), triazolam, dihydroergotamine, ergotamine, colchicine.

A medicinal preparation that is a substrate of the isoenzymes CYP2D6 and CYP3A4

Dextromethorphan

Amiodarone inhibits the isoenzymes CYP2D6 and CYP3A4 and can theoretically increase the plasma concentration of dextromethorphan.

Clopidogrel

Clopidogrel, which is an inactive thienopyrimidine drug, is metabolized in the liver with the formation of active metabolites.Possible interaction between clopidogrel and amiodarone, which can lead to a decrease in the effectiveness of clopidogrel.

The effect of other drugs on amiodarone

Inhibitors of CYP3A4 and CYP2C8 isoenzymes may have the potential to inhibit the metabolism of amiodarone and increase its concentration in the blood and, accordingly, its pharmacodynamic and side effects. It is recommended to avoid the intake of inhibitors of the isoenzyme CYP3A4 (for example, grapefruit juice and certain medications such as cimetidine, and HIV protease inhibitors (incl. indinavir)) during therapy with amiodarone. HIV protease inhibitors, when used simultaneously with amiodarone, can increase the concentration of amiodarone in the blood.

Inductors of the isoenzyme CYP3A4

Rifampicin

Rifampicin is a potent inducer of the isoenzyme CYP3A4, when combined with amiodarone it can reduce the plasma concentrations of amiodarone and desethylamiodarone.

Drug preparations of St. John's wort perfumed

St. John's wort is a strong inducer of the isoenzyme CYP3A4. In this regard, it is theoretically possible to reduce the plasma concentration of amiodarone and reduction of its effect (clinical data are absent).

Special instructions:

Since the side effects of Amiodarone are dose-dependent, patients should be treated with minimal effective doses in order to minimize the possibility of their occurrence.

Patients should be warned that during treatment they avoid exposure to direct sunlight or take protective measures (for example, the use of sunscreen, wearing appropriate clothing).

Monitoring of treatment

Before starting to take Amiodarone, it is recommended to perform an ECG test and determine the content of potassium in the blood. Hypokalemia should be corrected before starting Amiodarone. During treatment it is necessary to regularly monitor the ECG (every 3 months) and the level of transaminases and other indicators of liver function. In addition, due to the fact that Amiodarone may cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disease, prior to taking Amiodarone, clinical and laboratory (concentration of TSH in the blood serum,determined with the help of ultrasensitive analysis on TSH) examination for signs of thyroid dysfunction and diseases. During treatment with Amiodarone and for several months after discontinuation, the patient should be examined regularly for clinical or laboratory signs of a change in thyroid function. If there is a suspicion of a thyroid dysfunction, the serum TSH concentration should be determined (using an ultrasensitive TSH assay).

In patients receiving long-term treatment for rhythm disturbances, cases of increased ventricular defibrillation and / or an increase in the threshold of operation of a pacemaker or an implanted defibrillator, which may reduce the effectiveness of these devices. Therefore, before beginning or during treatment with Amiodarone, it is necessary to regularly check the correctness of their functioning.

Regardless of the presence or absence during the treatment with Amiodarone pulmonary symptoms, it is recommended that every 6 months, an X-ray examination of the lungs and pulmonary functional tests be performed.

The appearance of dyspnoea or dry cough, both isolated and accompanied by a worsening of the general condition (fatigue, weight loss, fever) may indicate pulmonary toxicity, such as interstitial pneumonitis, whose suspected development requires lung radiology and pulmonary functional tests.

Because of the prolongation of the repose period of the ventricles of the heart, the pharmacological effect of the drug Amiodarone causes certain changes in the ECG: prolongation of the QT interval, QTc(corrected), maybe the appearance of waves and. It is permissible to increase the interval (QTc not more than 450 ms, or no more than 25% of the initial value.) These changes are not a manifestation of the toxic effect of the drug, but require monitoring to correct the dose and evaluate the possible proarithmogenic effect of the drug Amiodarone.

With the development of atrioventricular blockade of II and III degree, sinoatrial blockade or a two-beam intraventricular blockade, treatment should be discontinued. When an atrioventricular block of degree I occurs, the observation should be strengthened.

Although there was an occurrence of arrhythmia or weighting of existing rhythm disturbances, sometimes fatal, the pro-arrhythmogenic effect of amiodarone is mild, less than most antiarrhythmic drugs, and is usually manifested in the context of factors that increase the duration of the QT interval, such as interaction with other drugs and / violations of the electrolytes in the blood (see the sections "Side effect" and "Interaction with other medicinal products"). Despite the ability of amiodarone to prolong the duration of the QT interval, it showed low activity with respect to provoking ventricular "pirouette" tachycardia.

With blurred vision or with reduced visual acuity, an ophthalmological examination, including examination of the fundus, should be performed urgently. With the development of neuropathy or optic neuritis caused by Amiodarone, the drug should be canceled because of the danger of developing blindness.

Because the amiodarone contains iodine, its use can disrupt the absorption of radioactive iodine and distort the results of a radioisotope study of the thyroid gland,However, taking the drug does not affect the reliability of determining the content of T3, T4 and TSH in blood plasma. Amiodarone inhibits the peripheral transformation of thyroxine (T4) into triiodothyronine (T3) and can cause isolated biochemical changes (increase in serum free T4, with a low or even normal concentration of free TK in serum) in clinically euthyroid patients, which is not the reason for withdrawal Amiodarone.

The development of hypothyroidism can be suspected when the following clinical signs appear, usually mild: weight gain, cold intolerance, decreased activity, excessive bradycardia (see section "Side effect"). Before surgery, the anesthesiologist should be informed of the patient's Amiodarone.

Prolonged treatment with the drug Amiodarone can enhance the hemodynamic risk inherent in local or general anesthesia.

In particular, this refers to its bradycardic and hypotensive effects, reduction of cardiac output and conduction disorders. In addition, in patients who took Amiodarone In rare cases, immediately after surgery, acute respiratory distress syndrome was noted. With the artificial ventilation of the lungs, such patients require careful monitoring.

It is recommended to carefully monitor the functional "liver" tests (monitoring the activity of "liver" transaminases) before the drug Amiodarone and regularly during drug treatment. When taking the drug Amiodarone possible acute violations of the liver (including hepatocellular insufficiency or liver failure, sometimes fatal) and chronic liver damage. Therefore, drug treatment Amiodarone should be terminated with an increase in the activity of "liver" transaminases, which is 3 times higher than the upper limit of the norm.

Clinical and laboratory signs of chronic liver failure when taking Amiodarone by mouth can be minimally expressed (hepatomegaly, increased activity of transaminases 5 times higher than the upper limit of the norm) and reversible after discontinuation of the drug, however, deaths have been reported in liver lesions.

Effect on the ability to drive transp. cf. and fur:

Based on safety data, there is no evidence that amiodarone violates the ability to drive vehicles or engage in other potentially hazardous activities. However, as a precautionary measure for patients with paroxysms of severe rhythm disturbances during drug treatment Amiodarone it is desirable to refrain from driving vehicles and practicing potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets 200 mg.

Packaging:

10 tablets per contour cell pack.

For 3 or 6 contour cell packs, along with instructions for medical use, put in a pack of cardboard.

Storage conditions:

In a place protected from light and moisture, at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002804

Date of registration:12.01.2015

Expiration Date:12.01.2020

The owner of the registration certificate:BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Manufacturer: & nbsp

BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Information update date: & nbsp09.08.2017

Illustrated instructions

Instructions

Amiodarone (Amiodaron)