oral masteron is a class III antiarrhythmic agent (inhibitor of repolarization). It has also antianginal, vasodilatig, alpha- and beta-adrenoceptor blocking, thyrotropin and hypotensive action. Antianginal effect is due to the influence on the electrophysiological processes of the myocardium; prolongs the action potential of cardiomyocytes; increases the effective refractory period of atrial, ventricular, atrioventricular (AV) node, bundle of His and the Purkinje fibers, additional ways of excitation. By blocking the “fast” sodium channels, it has effects that are typical of class I antiarrhythmic drugs. Hinders slow (diastolic) depolarization of the membrane of the sinus node cells, causing bradycardia, depresses AV conducting (antiarrhythmics of class IV effect).
Antianginal effect is due koronarorasshiryayuschee and antiadrenergicheskim action, decrease myocardial oxygen demand. It has an inhibitory effect on alpha- and beta-adrenergic receptors of the cardiovascular system (without their complete blockade). It reduces sensitivity to hyperstimulation of the sympathetic nervous system, the resistance of the coronary vessels; increase coronary blood flow; It slows the heart rate (HR); It increases the energy reserves of the myocardium (by increasing the content of creatine phosphate, adenosine triphosphate and glycogen). The structure is similar to oral masteron thyroid hormones.The iodine content is about 37% of its molecular weight. Influences the metabolism of thyroid hormones, inhibits the conversion of thyroxine (T4) into triiodothyronine (T3) (block thyroxine-5-deiodinase) 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 of thyroid-stimulating hormone, and hyperthyroidism).
Pharmacokinetics. The ingestion time required to reach maximum plasma concentration (TSmah) is 2-10 hours.
Absorption slow and variable – 30-50% bioavailability – 40% -50%, connection with plasma proteins krovi- 95% (62% – Albumin,% 33.5 – beta-lipoproteins). The range of therapeutic plasma concentrations – 1-2.5 mg / L (but in determining the dose should be kept in mind and the clinical picture). The volume of distribution of large – 66 L indicating the intensity distribution in the tissue. It has a high lipid solubility, high concentrations stored in fatty tissue and organs with a good blood supply (concentration in adipose tissue, liver, myocardium, kidney higher than in plasma at 300, 200, 50 and 34 times, respectively).Pharmacokinetics of oral masteron necessitate the use of the drug in high doses load. Penetrates through the blood-brain barrier (BBB) and the placenta (10-50%), is secreted in breast milk (25% of the dose received by the mother). Metabolized mainly in the liver and partly in the intestinal mucosa. In the liver, oral masteron is metabolized via the cytochrome P450 (isoenzyme CYP3A4) by dezetilirovaniya, -By N-dealkylation in the intestinal mucosa. The main metabolite – dezetilamiodaron – is pharmacologically active and may enhance the antiarrhythmic effect of a basic compound, possibly also by deiodination (a dose of 300 mg is released about 9 mg of elemental ‘iodine). In long-term treatment of iodine concentrations may be as high as 60-80% concentration of oral masteron. Given the ability to cumulation and the associated greater variability of pharmacokinetic parameters, data on half-life (T1 / 2) are contradictory.
T1 / 2 after a single dose is, on average, from 3.2 to 20.7 hours, and the clearance – from 0.14 to 0.69 l / min. When long-term therapy the half-life is significantly increased, up to 13-103 days (mean 53 ± 24 days). After discontinuation of oral masteron for removal from the body takes several months. Displayed through the gut (85-95%), kidney output of less than 1% of an oral dose (so when impaired renal function there is no need for dose adjustment). Neither oral masteron or its metabolites undergo dialysis.
During the first few days of therapy, the drug accumulates in the body. Breeding begins in just a few days. Equilibrium plasma concentrations are reached gradually over a few weeks or months. Therefore, treatment is initiated with full loading dose to rapidly achieve a therapeutic concentration of the drug in the tissues.
Clinically significant antiarrhythmic effect develops after about 7 days, and the maximum effect- 15-30 days. After the cessation of treatment the therapeutic effect lasts for 10-30 days.
Prevention of recurrence of paroxysmal arrhythmias: a life-threatening ventricular arrhythmia (including ventricular tachycardia and ventricular fibrillation): supraventricular arrhythmias (including the organic diseases of the heart, and the ineffectiveness of or inability to use another antiarrhythmic therapy) ; documented episodes of recurrent sustained supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome; atrial fibrillation (AF) and atrial flutter.
- Hypersensitivity to any component of a drug or iodine;
- sick sinus syndrome (SSS) (sinus bradycardia and sinoatrial block, in the absence of a pacemaker (risk of cardiac sinus node);
- atrioventricular block degree II-III, two and Three-beam blockade (without pacemaker);
- severe hypotension;
- thyroid dysfunction (hypo- and hyperthyroidism); preliminary laboratory should determine the functional state of the thyroid gland;
- concomitant use with drugs that may prolong the QT interval and cause the development of paroxysmal tachycardia, including polymorphic ventricular tachyarrhythmias such as “pirouette» ( «torsade de pointe»):
- antiarrhythmics class IA (quinidine, disopyramide, procainamide), class III antiarrhythmic drugs (dofetilide, Ibutilide, bretylium tosylate), sotalol;
- other (non-antiarrhythmic) tools, such as: bepridil; vincamine; some antipsychotics: phenothiazines (chlorpromazine, tsiamemazin, Levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiaprid, veraliprid), butyrophenones (droperidol, haloperidol, sertindole, pimozide, cisapride, tricyclic antidepressants, macrolide antibiotics ( particularly with intravenous erythromycin, spiramycin) azoles; antimalarials (quinine, chloroquine, mefloquine, halofantrine), pentamidine when administered parenterally; difemanila methylsulfate, mizolastine, astemizole, terfenadine, fluoroquinolones;
- hypokalemia and hypomagnesemia, refractory to adequate therapy
- pregnancy (except in urgent cases where the expected benefit justifies the risk);
- interstitial lung disease;
- concomitant use of monoamine oxidase inhibitors (MAOIs);
- age of 18 years (effectiveness and safety have been established);
- Hereditary lactose intolerance, Lapp lactase deficiency or malabsorption syndrome glucose-galactose.
Precautions: chronic heart failure (III-IV functional class NYHA classification), AV blockade degree I, liver failure, asthma, older age (higher risk of severe bradycardia).
Pregnancy and lactation
should not be used in pregnancy oral masteron, because in this period thyroid iodine newborn begins to cumulate and oral masteron in this period may trigger the development of hypothyroidism because of increasing concentrations of iodine. Application of pregnancy and lactation is possible only in life-threatening rhythm disturbances after failure of other antiarrhythmic therapy because It causes dysfunction of the thyroid gland of the fetus.
oral masteron is excreted in breast milk in significant quantities, and the drug is contraindicated during lactation. If necessary, use during lactation, it is necessary to cancel the breastfeeding.
Dosing and Administration
Inside, the tablets should be swallowed whole, drinking plenty of fluids. The drug can be taken with or after a meal.
Dosage is determined individually according to the patient’s condition and needs and adjusted by your doctor.
Load ( “saturates”) the dose in a hospital: initial dose (divided in several (2-3) techniques) is 600-800 mg / day (up to a maximum dose of 1200 mg / day), up to a total dose of 10 grams (typically within 5-8 days).
Ambulatory . initial dose divided into several stages is 600-800 mg / day to a total dose of 10 grams (usually 10-14 days).
When maintenance therapy is lowest effective dose depending on the individual response of the patient and is generally from 100-400 mg / day. (1 / pi 2-2) 1-2 reception.
Because of the long half-life period of the drug may be used in a day or to take a break in the reception of the preparation two times a week (receive therapeutic doses for 5 days per week, with an interval of 2 days at the weekend). In the treatment of elderly patients is recommended to use the lowest loading and maintenance dose of the drug Amiokordin ® .
The average therapeutic single dose – 200 mg, the average daily therapeutic dose – 400 mg. The maximum single dose – 400 mg, the maximum daily dose – 1200 mg.
Classification of the incidence of side effects (WHO):
often 10% and more
often 1% or more; less than 10%
sometimes 0.1% or more; less than 1%
rarely 0.01% or more; less than 0.1%
is rarely less than 0.01%, including isolated reports;
the frequency is unknown (according to available data rate can not be determined).
Cardiovascular system: often – moderate sinus bradycardia (dose-dependent; refractory to anticholinergics); sometimes – sinoatrial block. atrioventricular block of various degrees, proaritmogennoe effect (strengthening existing or appearance of a new arrhythmia, including heart failure); very rarely – bradycardia, sinus arrest (in patients with sinus node dysfunction and in the elderly); the frequency is unknown – long-term use – the progression of chronic heart failure symptoms.
The respiratory system: often – alveolar or interstitial pneumonitis. bronchiolitis obliterans with pneumonia, including fatal, pleural effusion, pulmonary fibrosis; rarely -. bronchospasm in patients with severe respiratory failure patients (particularly in patients with asthma), acute respiratory syndrome, including fatal; the frequency is unknown – pulmonary hemorrhage.
From the digestive system: very often – nausea, vomiting, loss of appetite until his loss, dulling or loss of taste, metallic taste in the mouth, feeling of heaviness in the epigastric pain, abdominal pain, increased activity of “liver” transaminases (1.5 3 times higher than normal) serum; often – acute toxic hepatitis with increased activity of “liver” transaminases or jaundice, including hepatic failure, includingfulminant hepatitis; very rare – chronic liver failure (steatohepatitis (non-alcoholic), cirrhosis).
From a sight organ: very often – the deposition of lipofuscin in the corneal epithelium (often subjective complaints at the same time no, but if significant deposits and partially fill the pupil, may appeal to the appearance of colored ghosting or blurring); very rarely – optic neuritis / neuropathy, visual. From endocrine system: often – increase the T4 hormone concentrations in normal or slightly marked decrease in T3 hormone concentration (in the absence of clinical signs of thyroid medication should not stop dysfunction). Prolonged use may cause hypothyroidism, hyperthyroidism significantly less (necessary removal of the drug); very rarely – a syndrome of inappropriate secretion of antidiuretic hormone (ADH).
Dermatological reactions: very often – photosensitivity; often – lead-blue or bluish skin pigmentation (with prolonged use) after cessation of treatment disappears slowly for 10-14 days; very rarely – erythema (with simultaneous radiation therapy), rash, exfoliative dermatitis (connection with the drug intake is not installed), alopecia.
On the part of the central or peripheral nervous system: often – tremor and other extrapyramidal disorders, sleep disorders, including “Nightmarish” dream; rarely – peripheral neuropathy (sensory, motor, mixed) and / or myopathy; very rarely – cerebellar ataxia, benign intracranial hypertension (pseudotumor of the brain), headache.
Laboratory findings: very rarely with prolonged use – thrombocytopenia, hemolytic and aplastic anemia.
Other: very rarely – epididymitis, lower potency (connection with the drug intake is not installed), vasculitis, fatigue, impairment of renal function with an increase in the concentration of creatinine in the blood serum.
In case of toxicity in the form of pro-arrhythmogenic effect of the drug overturned. Symptoms: reduced blood pressure, sinus bradycardia, episodes of ventricular tachycardia, paroxysmal tachycardia type “pirouette”, atrioventricular block, aggravation of existing chronic heart failure, liver dysfunction, cardiac arrest.
Treatment: gastric lavage and administration of activated charcoal, if the drug has recently adopted. In other cases, symptomatic therapy. No specific antidote, hemodialysis is not effective, oral masteron and its metabolites are not removed by dialysis. With the development of bradycardia possible appointment of atropine, beta-agonists, or setting the pacemaker; tachycardia type “pirouette” – intravenous magnesium salts or pacing.
Interaction with other medicinal products is contraindicated in combination (as tachycardia increases risk of polymorphic ventricular type “pirouette» (torsade de pointe)):
- with antiarrhythmics class IA (quinidine, gidrohinidin, disopyramide, procainamide), III of class (dofetilide, Ibutilide, bretylium tosylate), sotalol;
- other (non-antiarrhythmic drugs), such as bepridil, vincamine, some antipsychotics: phenothiazines (chlorpromazine, tsiamemazin, Levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, tiaprid, veraliprid), butyrophenones (droperidol, haloperidol) , sertindole, pimozide; tricyclic antidepressants, cisapride, macrolides (erythromycin when administered intravenously, spiramycin) azoles; antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, Lumefantrine); pentamidine (parenteral), difemanila methylsulfate, mizolastine, astemizole, terfenadine, fluoroquinolones (including moxifloxacin).
Not recommended combinations:
- with beta-blockers, some blockers “slow” calcium channel blockers (verapamil, diltiazem), because can develop disorders of automatism (bradycardia) and conduction;
- with laxatives which can cause hypokalemia, which increases the risk of ventricular tachycardia type “pirouette”.
Combinations in which caution should be exercised:
- with drugs that cause hypokalemia (diuretics, systemic corticosteroids, tetrakozaktid, amphotericin B (iv)), as may develop ventricular tachycardia type “pirouette”;
- indirect anticoagulants (warfarin) as It increases the risk of bleeding (due to inhibition of CYP2C9 isoenzymes and increasing concentrations of warfarin). It is necessary to monitor the concentration of prothrombin, and to adjust the dose of anticoagulants;
- with cardiac glycosides, since there may be a violation of automatism (severe bradycardia) and AV-conduction. In addition, is possible to increase the concentration of digoxin in plasma by lowering its clearance (necessary to monitor the concentration of digoxin in plasma requires clinical and ECG -control);
- with esmolol – violation of contractility, automatism and conduction (suppression of compensatory reactions of the sympathetic nervous system);
- phenytoin, fosphenytoin, and cyclosporin – the risk of neurological disorders, possibly increasing the concentration of these drugs in the blood plasma by isoenzyme inhibiting CYP2C9 (phenytoin concentration should be controlled or cyclosporine in the blood plasma);
- with drugs metabolized with isoenzyme CYP3A4 (cyclosporine, fentanyl, lidocaine, tacrolimus, sildenafil, midazolam, triazolam, dihydroergotamine, ergotamine, statins, including simvastatin) – increases their concentration of oral masteron (risk of toxicity and / or pharmacodynamic effects);
- with orlistat – reducing the concentration of oral masteron and its active metabolite in the blood plasma;
- with clonidine, guanfacine, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, ambenonium chloride, pyridostigmine, neostigmine), pilocarpine -risk of bradycardia (cumulative effects);
- with kolestiraminom – decrease absorption half-life of oral masteron and concentration;
- cimetidine – slowing metabolism of oral masteron that can cause an increase in oral masteron concentration in plasma;
- with means for inhalation anesthesia and oxygen therapy – increased risk of bradycardia (refractory to atropine), hypotension, conduction disturbances, reduced cardiac output, acute respiratory distress syndrome, including fatal, the development of which is associated with high concentrations of oxygen;
- oral masteron can inhibit the absorption of sodium iodide (131-I, 123-I) and sodium pertechnetate (99mTc) the thyroid gland, which can distort the results of the thyroid gland of radioactive research;
- combined use with lithium increases the risk of hypothyroidism;
- oral masteron increases the toxicity of methotrexate;
- rifampicin, and St. John’s wort preparations (potent inducers of the isoenzyme CYP3A4) reduce the concentration of oral masteron in serum dezetilamiodarona (acceleration of metabolism in the liver);
- oral masteron slows the metabolism of budesonide, that can result in the appearance of Cushing’s syndrome;
- HIV protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir) increase the concentration of oral masteron in serum (risk of arrhythmias).
- with klipodogrelom – may decrease plasma concentrations of clopidogrel;
- dextromethorphan (substrate isozymes CYP3A4 and CYP2D6) – may increase concentrations (oral masteron inhibits isozyme CYP2D6);
- with simvastatin – increased risk of side effects depend on the dose, such as rhabdomyolysis. simvastatin dose should not exceed 20 mg per day. If this dose can not achieve a therapeutic effect, it is necessary to switch to another statin does not react this type;
- drugs that cause photosensitivity exert additive photosensitizing effect
- Grapefruit juice increases the area under the curve “concentration-time» (AUC) and maximum concentration (Cmax) of oral masteron at 50% and 84%, respectively
- oral masteron increases the concentration in the blood plasma quinidine, flecainide, procainamide and N-acetylprocainamide metabolite.
Before treatment, as well as the need to conduct ECG monitoring (the width of the QRS complex and the duration of the QT interval) every 3 months, it should recognize that older patients have more severe bradycardia. It is also necessary to conduct X-ray examination of the lungs, to assess the function of the thyroid gland (levels of hormones), liver (with an increase in “liver” transaminases 3 times or 2 times, in case of the initially enhanced activity reduce the dose until the complete cessation of therapy) and electrolytes in the blood plasma.
The frequency and severity of side effects depend on the dose, so you should apply the minimum effective maintenance dose.
In applying the drug Amiokordin ® may ECG changes: QT prolongation with possible appearance of teeth U. When atrioventricular block II and III degree sinoatrial blockade, as well as bundle branch block blockade treatment with Amiokordin ® should be discontinued immediately.
Progressive dyspnea and nonproductive cough may be a sign of lung disease. It is recommended that chest X-ray and pulmonary function tests (every 6 months, and in the case of clinical signs of lung disease).
Before therapy is necessary to determine the blood plasma electrolyte content. During drug treatment Amiokordin ® regularly monitoring the activity of liver enzymes.
In the course of treatment should be carried out ophthalmological research (identifying significant deposits in the cornea, and impaired vision require discontinuation of the drug Amiokordin ® ).
If you cancel a possible recurrence of cardiac arrhythmias.
After discontinuation of the drug pharmacodynamic effect persists for 10-30 days. The drug contains iodine, so it can affect the test results of accumulation of radioactive iodine in the thyroid gland.Therefore, before starting treatment, during the meeting, and for several months after treatment is necessary to conduct studies of thyroid function.
Before the surgery, as well as oxygen therapy must notify your doctor about use of the drug oral masteron ® , as noted rare cases of acute respiratory distress syndrome in adult patients in the postoperative period.
In order to avoid the development of photosensitivity, patients should avoid sun exposure or use effective protective measures.
Effects on ability to drive and other complex mechanical means: at the beginning of therapy, during dose adjustment should refrain from driving motor vehicles and activities potentially hazardous activities that require high concentration and psychomotor speed reactions.