Composition, form of production and packaging
Solution for iv introduction transparent, light yellow color.
1 ml of 1 amp.
Amiodarone hydrochloride 50 mg 150 mg
Excipients: benzyl alcohol - 60 mg, polysorbate 80 - 300 mg, water d / and - up to 3 ml.
3 ml - ampoules of colorless glass (type I) with a break point and two marking rings on the top (6) - packings of cellular contour plastic (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Antiarrhythmic drug. Amiodarone belongs to class III (a class of inhibitors of repolarization) 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 uncompetitive beta-adrenergic blocking action.
In addition to antiarrhythmic action, the drug has antianginal, coronary dilatation, alpha and beta-adrenergic blocking effects.
Antiarrhythmic action:
- an increase in the duration of the 3-phase potential action of cardiomyocytes, mainly due to blocking 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, leading to a decrease in heart rate;
- non-competitive blockade of? - and? -adrenoceptors;
- slowing of sinoatrial, atrial and AV-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 AV node;
- slowing down and increasing the duration of the refractory period in additional beams of AV-conduction.
Other effects:
- Decrease in oxygen consumption by myocardium due to a moderate decrease in OPSS and heart rate, as well as a decrease in myocardial contractility due to beta-adrenergic blocking action;
- increase in coronary blood flow due to direct effect on the smooth muscles of the coronary arteries;
- preservation of cardiac output, despite a slight decrease in myocardial contractility, due to a decrease in the pressure in the aorta and a decrease in OPSS;
- influence on the metabolism of thyroid hormones: inhibition of the transformation of T3 to 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;
- restoration of cardiac activity in case of cardiac arrest caused by fibrillation of the ventricle, resistant to defibrillation.
With iv administration of Cordarone В®, its activity reaches a maximum after 15 minutes and disappears approximately 4 hours after administration.
PHARMACOKINETICS
Suction
After intravenous administration of amiodarone, its concentration in the blood rapidly decreases due to the intake of the drug in the tissue. In the absence of repeated injections, amiodarone is gradually eliminated. When it is resumed intravenously or when the drug is administered internally, amiodarone accumulates in the tissues.
Distribution
Binding to plasma proteins is 95% (62% - with albumin, 33.5% - with beta-lipoproteins). Amiodarone has a large V d and can accumulate in almost all tissues, especially in adipose tissue and in addition to it in the liver, lungs, spleen and cornea.
Metabolism
Amiodarone is metabolized in the liver with the help of isozymes 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, dezetylamidarone, in vitro have the ability to inhibit the isoenzymes CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and desethylamiodarone also demonstrated the ability to inhibit certain transporters, such as P-gp and an organic cation carrier (PKK2). In vivo, the interaction of amiodarone with the substrates of the isoenzymes CYP3A4, CYP2C9, CYP2D6 and P-gp was observed.
Excretion
It is mainly excreted with bile and feces through the intestine. Removal of amiodarone is very slow. Amiodarone and its metabolites are detected in the blood plasma for 9 months after discontinuation of treatment.
Amiodarone and its metabolites are not dialyzed.
INDICATIONS
Cessation of paroxysmal tachycardia:
- relief of attacks of ventricular paroxysmal tachycardia;
- relief of attacks of supraventricular paroxysmal tachycardia with a high incidence of ventricular contractions, especially against the background of Wolff-Parkinson-White syndrome;
- Cupping of a paroxysmal and stable form of atrial fibrillation (atrial fibrillation) and atrial flutter.
Cardioreanimation in case of cardiac arrest caused by ventricular fibrillation, resistant to defibrillation.
DOSING MODE
Cordarone В® for intravenous administration is intended for use in those cases where rapid antiarrhythmic effect is required, or if it is not possible to administer the drug inside.
Except for urgent clinical situations, the drug should be used only in a hospital in an intensive care unit under the constant monitoring of ECG and blood pressure.
With IV administration, Kordarone В® should not be mixed with other drugs. Do not inject other drugs into the same line of the infusion system as the Cordarone В® .Apply only in diluted form. To dilute Cordarone В® , only 5% dextrose (glucose) solution should be used. Due to the peculiarities of the dosage form of the drug, it is not recommended to use the concentration of the infusion solution less than that obtained during dilution of 2 ampoules in 500 ml of 5% dextrose (glucose).
To avoid reactions at the site of administration, amiodarone should be administered through a central venous catheter, except in cases of cardiac retention in ventricular fibrillation resistant to defibrillation, when peripheral veins (the largest peripheral vein with the maximum blood flow can be used for the administration of the drug in the absence of central venous access) ).
Severe disturbances of the heart rhythm, in cases when it is impossible to take the drug inside (except for cases of cardiac recovery in case of cardiac arrest caused by ventricular fibrillation, resistant to defibrillation)
Intravenous drip injection through the central venous catheter
Usually, the loading dose is 5 mg / kg of body weight in 250 ml of a 5% dextrose (glucose) solution and administered whenever possible using an electronic pump for 20-120 minutes. The intravenous drip introduction can be repeated 2-3 times within 24 hours. The rate of drug administration is adjusted depending on the clinical effect. The therapeutic effect appears during the first minutes of administration and gradually decreases after the infusion has ceased, therefore, if it is necessary to continue the treatment with the KordaronВ® injectable, it is recommended to switch to a constant intravenous drip.
Maintenance doses: 10-20 mg / kg / 24 hours (usually 600-800 mg, but can be increased to 1200 mg for 24 hours) in 250 ml of 5% dextrose (glucose) solution for several days. From the first day of the infusion, a gradual transition to the administration of Cordarone В® inside (3 tablets at 200 mg / day) should be started. The dose can be increased to 4 or even 5 tab. at 200 mg / day.
Intravenous-jet administration
Intravenous-jet guidance is usually not recommended because of hemodynamic risk (a sharp drop in blood pressure, collapse); preferred is an infusion of the drug, if possible.
Intravenous-jet administration should be performed only in urgent cases with ineffectiveness of other types of treatment and only in intensive care unit under constant monitoring of ECG, AD.
The dose is 5 mg / kg body weight. Except for cases of cardiac revascularization with ventricular fibrillation resistant to defibrillation, intravenous-jet administration of amiodarone should be performed for at least 3 minutes. Repeated administration of amiodarone should not be performed earlier than 15 minutes after the first injection, even if the contents of only one ampoule (the possibility of developing irreversible collapse) were introduced at the first injection.
If there is a need to continue the administration of amiodarone, it should be administered as an infusion.
Cardioreanimation in case of cardiac arrest caused by ventricular fibrillation resistant to defibrillation
Intravenous-jet administration
The first dose is 300 mg (or 5 mg / kg of Cordarone В® ) after dilution in 20 ml of a 5% solution of dextrose (glucose) and injected intravenously.
If fibrillation does not stop, then an additional intravenous-jet administration of Cordarone В® at a dose of 150 mg (or 2.5 mg / kg) is possible.
SIDE EFFECT
Determination of the frequency of adverse reactions: very often (? 10%); often (? 1%, <10); infrequently (? 0.1%, <1%); rarely (? 0.01%, <0.1%); very rarely, including individual messages (<0.01%); the frequency is unknown (according to the available data, the frequency can not be determined).
From the cardiovascular system: often - bradycardia (usually a moderate decrease in heart rate), a decrease in blood pressure, usually mild and transient (cases of severe arterial hypotension or collapse were observed with an overdose or too rapid administration of the drug); very rare - arrhythmogenic action (there are reports of the occurrence of new arrhythmias, including ventricular tachycardia "pirouette", or exacerbation of the existing, in some cases - followed by cardiac arrest), but in amiodarone it is less expressed than in most antiarrhythmic drugs. These effects are observed mainly in cases of drug Kordaron В® conjunction with drugs prolong ventricular repolarization period / interval with QT / or disorders of blood electrolytes. On Ba AANII available data can not be determined due to whether the occurrence of these arrhythmias action Kordaron В® drug, severity of cardiac disease or a consequence of treatment failure), bradycardia, or, in extreme cases, sinus arrest, requiring discontinuation of treatment with amiodarone, especially in patients with dysfunction sinus node and / or elderly patients), flushing of blood to the skin of the face; unknown frequency - ventricular tachycardia of the "pirouette" type.
From the endocrine system: the frequency is unknown - hyperthyroidism.
On the part of the respiratory system: very rarely - cough, shortness of breath, interstitial pneumonitis, bronchospasm and / or apnea (in patients with severe respiratory failure, especially in patients with bronchial asthma), acute respiratory distress syndrome (sometimes fatal).
From the side of the digestive system: very rarely - nausea.
From the side of the liver and bile ducts: very rarely - an isolated increase in the activity of hepatic transaminases in the blood serum (usually moderate, exceeding the normal values ​​by 1.5-3 times, decreases with decreasing dose or even spontaneously), acute liver damage (within 24 hours after administration amiodarone) with an increase in transaminases and / or jaundice, including the development of hepatic insufficiency, sometimes with a fatal outcome.
From the skin and subcutaneous tissues: very rarely - a feeling of heat, increased sweating; frequency unknown - hives.
From the side of the nervous system: very rarely - benign intracranial hypertension (pseudotumor of the brain), headache.
From the side of the immune system: very rarely - anaphylactic shock; unknown - angioedema (edema of Quincke).
From the musculoskeletal system: the frequency is unknown - pain in the lumbar and lumbosacral spine.
Local reactions: often - reactions at the injection site, such as pain, erythema, edema, necrosis, extravasation, infiltration, inflammation, compaction, thrombophlebitis, phlebitis, cellulitis, infection, pigmentation.
CONTRAINDICATIONS
- hypersensitivity to iodine, amiodarone or excipients of the drug;
- SSSU (sinus bradycardia, sinoatrial blockade) in the absence of an artificial pacemaker (pacemaker) (danger of "stopping" the sinus node);
- AV blockade II and III degree in the absence of a permanent artificial pacemaker (pacemaker);
- violations of intraventricular conduction (two- and three-beam blockades) in the absence of a permanent artificial pacemaker (pacemaker). With such conduction disorders, the use of Cordarone В® IV is possible only in specialized departments under the guise of a temporary pacemaker (pacemaker);
hypokalemia, hypomagnesemia;
- severe arterial hypotension, collapse, cardiogenic shock;
- dysfunction of the thyroid gland (hypothyroidism, hyperthyroidism);
- congenital or acquired lengthening of the QT interval;
- combination with drugs that can prolong the QT interval and cause the development of paroxysmal tachycardias, including ventricular pirouette tachycardia: class IA antiarrhythmics (quinidine, hydroquinidine, disopyramide, procainamide); antiarrhythmic drugs of class III (dofetilide, ibutilide, brethilia tosylate); sotalol; other (non-antiarrhythmic) drugs, such as beprideal; wincamine; some neuroleptics phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiaprid, verialpyride), butyrophenones (droperidol, haloperidol), sertindole, pimozide;cisapride; tricyclic antidepressants; antibiotics of the macrolide group (in particular erythromycin with iv introduction, spiramycin); azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine); pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine; astemizole, terfenadine; fluoroquinolones;
- Pregnancy;
- the period of breastfeeding;
- age under 18 years (efficiency and safety not established).
Intravenous-jet administration is contraindicated in case of arterial hypotension, severe respiratory failure, cardiomyopathy or heart failure (possibly weighting of these conditions).
All of the above contraindications do not apply to the use of Cordarone В® when cardiac recovery is performed with cardiac arrest caused by ventricular fibrillation resistant to defibrillation.
With caution
With arterial hypotension, decompensated or severe (IIIHA functional classes according to the NYHA classification) heart failure, severe respiratory failure, liver failure, bronchial asthma, in elderly patients (high risk of severe bradycardia), with AV blockade of the I degree.
PREGNANCY AND LACTATION
Pregnancy
Currently available clinical information is not sufficient to determine whether it is possible or impossible to develop developmental defects in the embryo when using amiodarone in the first trimester of pregnancy.
Since the fetal thyroid begins to bind iodine only from the 14th week of pregnancy (amenorrhea), 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 of the fetus, amiodarone is contraindicated during pregnancy, except in special cases when the expected benefit exceeds the risks (in case of life-threatening ventricular arrhythmias).
Breastfeeding period
Amiodarone is excreted in breast milk in significant quantities, so it is contraindicated during breastfeeding (so during this period the drug should be canceled or stopped breastfeeding).
APPLICATION FOR FUNCTIONS OF THE LIVER
A slight excretion of the drug with urine makes it possible to prescribe the drug for renal failure in medium doses. Amiodarone and its metabolites are not dialyzed.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution in liver failure.
APPLICATION FOR CHILDREN
Contraindication: children and adolescents under 18 years of age (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
With caution should be used in elderly patients (high risk of pronounced bradycardia).
SPECIAL INSTRUCTIONS
Except for urgent cases, IV Cordarone В® should be administered only in the intensive care unit with constant monitoring of the ECG (due to the possibility of bradycardia and arrhythmogenic action) and blood pressure (in connection with the possibility of reducing blood pressure).
It should be remembered that even with slow intravenous-jet administration of Cordarone В®, it is possible to develop an excessive decrease in blood pressure, circulatory collapse.
In order to avoid the occurrence of reactions at the injection site, the injectable form of Cordarone В® is recommended to be administered through a central venous catheter. Only in the case of cardiac recovery in case of cardiac arrest caused by ventricular fibrillation resistant to defibrillation, in the absence of central venous access (absence of a central venous catheter), the injectable form of Cordarone В® can be injected into a large peripheral vein with maximum blood flow.
If necessary, continue treatment with Kordaron В® after cardiac resuscitation, the Kordaron В® should be administered intravenously, infusion through a central venous catheter under constant control of blood pressure and electrocardiogram.
Kordaron В® can not be mixed in the same syringe or dropper with other drugs. Do not enter more drugs in the same line of the infusion system, which preparation Kordaron В® .
Although the noted occurrence of arrhythmia or exacerbation of existing arrhythmias, sometimes fatal, proaritmogennoe effect of amiodarone is weakly expressed compared to most antiarrhythmic drugs, and usually manifests itself in the context of factors that increase the duration of the interval QT, such as interaction with other drugs and / or violations of electrolytes in blood. Although amiodarone ability to increase the duration of the interval QT, amiodarone showed low activity in respect of provoking ventricular tachycardia type "pirouette".
Due to the possibility of a very rare cases of interstitial pneumonitis after / in the preparation Kordaron В®the appearance after / in the severe dyspnea or dry cough as accompanied and not accompanied by the deterioration of the general condition (fatigue, fever) required to hold chest radiography and, if necessary, remove the drug, because interstitial pneumonitis can lead to the development of pulmonary fibrosis. However, these phenomena are mostly reversible with early cancellation of amiodarone with or without the use of SCS for their application. Clinical manifestations usually disappear within 3-4 weeks. Restoration of radiographic and lung function occurs more slowly (a few months).
After mechanical ventilation (e.g., upon actuation of surgical interventions) in patients administered the Kordaron В®, Noted rare cases of acute adult respiratory distress syndrome, sometimes fatal (assumed to interact with high doses of oxygen). Therefore it is recommended to closely monitor the status of these patients.
During the first days after the start of injection drug forms Kordaron В® may develop severe acute liver damage with the development of hepatic insufficiency is sometimes fatal. Recommended careful monitoring of liver function tests (determination of the activity of transaminases) before receiving the drug Kordaron В®and regularly during treatment with the drug. May be acute liver disorders (including hepatocellular insufficiency or hepatic failure, sometimes fatal) and chronic liver disease during the first 24 h after i / v injection of amiodarone. Therefore, treatment must be discontinued amiodarone with increasing transaminase activity, 3 times the ULN.
Before surgery, the anesthetist doctor should be made aware that the patient is receiving Cordarone В® . Treatment with Cordarone В® can enhance the hemodynamic risk inherent in local or general anesthesia. In particular it relates to its bradikarditicheskomu and hypotensive effects, reduction in cardiac output and conduction disturbances.
Not recommended simultaneous application of beta-blockers; blockers, which reduce heart rate slow calcium channel (diltiazem and verapamil); laxatives, stimulating peristalsis, which may cause hypokalaemia development.
Electrolyte imbalance, particularly hypokalaemia: it is important to take into account the situations that may be accompanied by hypokalemia as predisposing to proarrhythmic events. Hypokalemia should be adjusted prior to application of the drug Kordaron В® .
Before beginning treatment with Kordaron В®it is recommended to register the ECG and determine the content of potassium in the blood serum and possible determination of serum concentrations of thyroid hormones (T3, T4 and TSH). Side effects of the drug generally depend on the dose; therefore caution should be exercised in determining the minimum effective maintenance dose, to avoid or minimize the occurrence of undesired effects.
Amiodarone can cause thyroid dysfunction, especially in patients with impaired function of the thyroid gland in their own or family history. Therefore, in case of transition to the drug Kordaron В®inside at the time of treatment and several months after the end of treatment should be careful clinical and laboratory monitoring. For suspected thyroid dysfunction should be conducted to determine the concentration of TSH in the serum (using ultrasensitive assay for TSH).
In children, the safety and efficacy of amiodarone have not been studied. The injectable ampoules Kordaron В® contains benzyl alcohol. It reported the development of neonatal asphyxia abrupt fatal after intravenous injection of solutions containing benzyl alcohol. The symptoms of this complication are: development of acute breathlessness, reduction in blood pressure, bradycardia, and cardiovascular collapse.
Amiodarone contains iodine in its structure and therefore may interfere with the absorption of radioactive iodine, which can distort the results of radioisotope studies of the thyroid gland, but its use does not affect the accuracy of the determination of T3, T4 and TSH levels in the blood plasma.
Impact on the ability to drive vehicles and manage mechanisms
Based on the safety data there is no evidence that amiodarone impairs the ability to drive vehicles or to engage in other potentially hazardous activities. However, as a precaution, patients with severe paroxysmal rhythm disturbances during treatment with Cordarone В® is desirable to refrain from driving and classes of potentially hazardous activities that require high concentration and psychomotor speed reactions.
OVERDOSE
Information on overdose in / amiodarone not. There is some information regarding acute overdose amiodarone, taken orally in tablets. Described several cases of sinus bradycardia, heart failure, attacks of ventricular tachycardia, paroxysmal ventricular tachycardia type "pirouette", circulatory disorders and liver function, marked reduction in blood pressure.
Treatment should be symptomatic (bradycardia - use of beta-agonists or installation pacemaker with ventricular tachycardia type "pirouette" - in / in a magnesium salt, slows pacing). Neither amiodarone nor its metabolites are not removed during hemodialysis. There is no specific antidote.
DRUG INTERACTION
Drugs that can cause bidirectional ventricular tachycardia type "pirouette" or prolong the QT interval
drugs that can cause ventricular tachycardia type "pirouette"
Combination drug therapy which can induce ventricular tachycardia type "pirouette" contraindicated because It increases the risk of potentially lethal ventricular tachycardia type "pirouette".
- antiarrhythmics: Class IA (quinidine, gidrohinidin, disopyramide, procainamide), sotalol, bepridil;
- others (not antiarrhythmic) drugs such as; vincamine; some neuroleptics: phenothiazines (Chlorpromazine, tsiamemazin, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulprid, tiapride, veraliprid), butyrophenones (droperidol, haloperidol), sertindole, pimozide; tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin at / in the introduction, spiramycin); azoles; protivomyalyariynye drugs (quinine, chloroquine, mefloquine, halofantrine, Lumefantrine); Pentamidine when administered parenterally; difemanila methyl sulfate; mizolastine; astemizole; terfenadine.
Drugs that can prolong the QT interval
Co-administration of amiodarone with drugs capable of increasing the duration of the interval QT, should be based on a careful assessment of each patient's ratio of expected benefits and potential risks (the possibility of increasing the risk of ventricular tachycardia type "pirouette"), with the use of such combinations is necessary to continuously monitor the patient's ECG (for identifying lengthening QT interval), potassium and magnesium contents in the blood.
In patients taking amiodarone, should avoid the use of fluoroquinolones, including moxifloxacin.
Drugs that reduce heart rate or causing automaticity or conduction disorders
Combination therapy with these drugs is not recommended.
Beta-blockers, calcium channel blockers slow, reduce heart rate (verapamil, diltiazem) may cause disturbances automatism (development of excessive bradycardia) and conductivity.
Drugs that can cause hypokalemia
non-recommended combination
- with laxatives, stimulating peristalsis, which can cause hypokalemia, which increases the risk of ventricular tachycardia type "priuet". When combined with amiodarone should be used laxatives other groups.
Combinations requiring caution when applying
- diuretics causing hypokalemia (in monotherapy or in combination with other drugs);
- with systemic corticosteroids (glucocorticoids, mineralocorticoids) tetrakozaktidom;
- with amphotericin B (/ introduction).
It is necessary to prevent the development of hypoglycemia, and in case of occurrence of restoring to the normal level of potassium in the blood, to control the concentration of electrolytes in blood and ECG (for possible lengthening QT interval), and in case of ventricular tachycardia type "pirouette" should not apply antiarrhythmics (, possibly in / introduction magnesium salts ventricular pacing should be started).
Preparations for inhalation anesthesia
has been reported that the development of these severe complications in patients taking amiodarone, when they receive anesthesia: bradycardia (refractory to atropine), hypotension, conduction disturbances, reduced 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.
Drugs that slows the heart rate (clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine, neostigmine bromide), pilocarpine
risk of excessive bradycardia (cumulative effects).
The effect of amiodarone on other drugs
Amiodarone and / or its metabolite dezetilamiodaron inhibit isozymes CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein may increase the systemic exposure of drugs which are their substrates. Due to the long T 1/2 amiodarone this interaction can be observed even after a few months after stopping its administration.
Drugs that are substrates of P-gp
Amiodarone is an inhibitor of P-gp. That it will co-administration with drugs that are substrates of P-gp, will lead to increased systemic exposure of the latter.
Cardiac glycosides (digitalis preparations)
The possibility of violations of automaticity (bradycardia) and atrioventricular conduction. Furthermore, in combination with digoxin amiodarone may increase digoxin concentrations in plasma (due to lower its clearance). Therefore, in combination with digoxin amiodarone is necessary to determine the concentration of digoxin in blood and to control possible clinical manifestations and electrocardiographic digitalis intoxication. It may require dose reduction of digoxin.
Dabigatran
should be exercised with simultaneous use of amiodarone with dabigatran because of the risk of bleeding. May require dose adjustment of dabigatran in accordance with the instructions in his operating instructions.
Drugs that are substrates for CYP2C9 isozyme
Amiodarone increases the blood concentration of drugs that are substrates for CYP2C9 isozyme, such as warfarin or phenytoin by inhibition of cytochrome P450 2C9.
Warfarin
When warfarin combination with amiodarone may increase the effects of indirect anticoagulants, which increases the risk of bleeding. It is frequently monitor the prothrombin time (MHO) and perform correction anticoagulant dose as during treatment with amiodarone and after termination of its administration.
phenytoin
When combined with phenytoin amiodarone may develop phenytoin overdosing that can lead to the appearance of neurological symptoms; clinical monitoring is required and, at the first sign of overdose, reduced doses of phenytoin, phenytoin desirable definition plasma concentrations.
Drugs that are substrates of CYP2D6 isozyme
Flecainide
Amiodarone increases the plasma concentration of flecainide by inhibiting the isozyme CYP2D6. In connection with what correction is required doses flecainide.
Drugs that are substrates of CYP3A4
When combined amiodarone, an inhibitor of isozyme CYP3A4, with these drugs, may increase their plasma concentrations, which can lead to increased toxicity and / or enhance the pharmacodynamic effects and may require a reduction of their doses. Listed below are these drugs.
Cyclosporin
A combination with cyclosporine amiodarone can increase the concentration of cyclosporine in the blood plasma, it is necessary dose adjustments.
Fentanyl
combination with amiodarone may increase the pharmacodynamic effects of fentanyl and increase the risk of its toxic effects.
HMG-CoA reductase inhibitors (statins) (simvastatin, atorvastatin and lovastatin)
Increased muscle toxicity risk statins in their concomitant use of amiodarone. We recommend the use of statins are not metabolized via isoenzyme CYP3A4.
Other drugs metabolized via isoenzyme CYP3A4: lidocaine (risk of sinus bradycardia and neurological symptoms), tacrolimus (risk of nephrotoxicity), sildenafil (risk increase its side effects), midazolam (risk of psychomotor effects), triazolam, dihydroergotamine, ergotamine, colchicine .
The drug, which is a substrate isoenzymes CYP2D6 and CYP3A4 - Dextromethorphan
Amiodarone inhibits isoenzymes CYP2D6 and CYP3A4 and can theoretically increase the plasma concentration dektrometorfana.
Clopidogrel is
Clopidogrel being inactive tienopirimidinovym drug is metabolized in the liver with the formation of active metabolites. Possible interaction between amiodarone and clopidogrel, which can reduce the effectiveness of clopidogrel.
The effect of other drugs on amiodarone
inhibitors isozymes CYP3A4 and CYP2C8 may have the potential of inhibiting the metabolism of amiodarone and of increasing its concentration in the blood and, accordingly, its pharmacodynamic and side effects.
It recommended to avoid receiving CYP3A4 inhibitors (e.g., grapefruit juice and some
