Concentrate for the preparation of a solution for intravenous administration in the form of a transparent, slightly colored liquid.
4-Nitro-N - [(1RS) -1- (4-fluorophenyl) -2- (1-ethylpiperidin-4-yl) ethyl] benzamide hydrochloride 1 mg
[PRING] citric acid monohydrate 0.33 mg, sodium citrate dihydrate 6.49 mg, polysorbate 80 2 mg, water d / and up to 1 ml.
2 ml - ampoules (3) - packings of cellular contour (1) - packs cardboard.
2 ml - ampoules (5) - packings of cellular contour (1) - packs cardboard.
2 ml - ampoules (5) - packings, cellular outline (2) - packs cardboard.
2 ml - ampoules (5) - packings of cellular contour (5) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
The main mechanism of action of the drug Refralon is the suppression of the outflowing potassium current of delayed rectification, which leads to an extension of the repolarization phase of the action potential and to an extension of the refractory periods of the heart fibers. It is the elongation of the refractory periods of the myocardium that is the mechanism of antiarrhythmic action of III class drugs. Refralon does not significantly affect the automatism of the sinus node, it does not slow down the rate of impulses along the conduction system of the heart, including the atriovieticular node. The drug does not affect the intervals of PQ and QRS in complexes of sinus origin. However, the effect of the drug may be accompanied by a frequency-dependent violation of intraventricular conduction in the form of aberrant ventricular complexes in response to premature atrial impulses. The main electrocardiographic manifestation of the drug is the prolongation of the QT and QTc intervals. In some cases, the appearance of a wave U can be observed.
Antiarrhythmic effect (arresting arrhythmia) can develop immediately after the introduction of the first dose of the drug, but may be delayed and with respect to the time of administration of repeated doses. The duration of the QT (QTc) interval, the main indicator of the pharmacological effect of the drug and its safety control, begins to increase already during the administration of the solution, and after its termination reaches a maximum of 15 minutes from the onset of administration. After that, it varies little from 1 hour to 6-7 hours, depending on the total dose of the drug administered. In the future, the duration of the QT interval (QTc) gradually decreases, reaching normal values вЂ‹вЂ‹in terms of 3 to 24 hours, depending on the dose and individual response of the patient. In therapeutic doses, the drug does not affect blood pressure, does not adversely affect the basic systems and functions of the body. It does not cause allergic reactions, does not have mutagenic and teratogenic properties, is not carcinogenic and does not have an embryotoxic effect.
The drug Refralon with intravenous injection quickly disappears from the bloodstream with a half-distribution period of 5.13 minutes. The time of half-elimination from the blood was 23.3 minutes. The drug very quickly penetrates into such organs as the liver, kidneys, heart. Cumulation in these organs was not observed. The period of semi-elimination of the drug from the organs was about 1 hour. The drug in the brain tissues is not found. With intravenous administration, the drug is excreted in the urine both in unchanged form and in the form of metabolites. The preparation is absent in feces.
Data on the metabolism of the drug show that its biotransformation goes along the path of de-ethylation, reduction of the NO2-group to NH2, followed by acetylation.
- Coping of atrial fibrillation and flutter, including for medicamentous cardioversion of a persistent form (duration of more than 7 days) of these arrhythmias.
For intravenous administration only.
Introduction of the drug Refralon should be performed in the intensive care unit, followed by observation for 24 hours under continuous ECG monitoring to detect possible adverse events in a timely manner. Prior to the administration of the drug and after the administration of each of the consecutive doses of the preparation, it is necessary to register the ECG in 12 leads to monitor the heart rate, the duration of the QRS, QT, QTc intervals. Before use, the preparation Refralon should be diluted in 20 ml of 0.9% sodium chloride solution.
The preparation is administered in three consecutive stages:
вЂў administration in a dose of 10 Ојg per 1 kg of body weight, intravenously for 2-3 minutes;
вЂў in the absence of effect (no restoration of sinus rhythm) after 15 minutes repeated intravenous injection at a dose of 10 Ојg per 1 kg of body weight (total dose of the drug 20 Ојg / kg body weight);
вЂў in the absence of effect (no recovery of the sinus rhythm) after 15 minutes, repeated intravenous injection at a dose of 10 Ојg per 1 kg of body weight (maximum total dose of the drug 30 Ојg / kg body weight).
The drug is discontinued at any stage in the case of:
вЂў restoration of sinus rhythm;
вЂў reduction of heart rate <50 bpm;
вЂў increasing the duration of the interval QT> 500 ms;
вЂў development of proarrhythmic effects.
On the part of the cardiovascular system: a decrease in heart rate on a background of a sinus rhythm of less than 50 beats / min, an increase in the duration of the interval QT> 500 ms, the occurrence of ventricular arrhythmias.
On the part of laboratory indicators: increased activity of aspartate and alanine aminotransferase.
During the introduction of the drug, a "feeling of heat" may appear.
The patient should be warned about the need to inform the doctor about any unusual sensations during the administration of the drug.
- congenital or acquired lengthening of QT interval on surface ECG more than 440 ms;
- bradysystolic form of atrial fibrillation or flutter with heart rate <50 beats. in minutes or pauses> 3 seconds, recorded on an ECG or detected by the results of a daily monitoring of the ECG by Holter;
- syndrome of weakness of the sinus node (sinus bradycardia, sinoatrial block) recorded earlier on the background of a sinus rhythm, except for cases of their correction by an artificial pacemaker (pacemaker);
- atrioventricular blockade of II-III degree, two- and three-beam blockade in the absence of an artificial pacemaker (pacemaker);
- age under 18 years (effectiveness and safety not studied);
- acute coronary syndrome (efficacy and safety not studied);
Decompensated or severe chronic heart failure (NYHA class III-IV functional class) (efficacy and safety not studied);
- bronchial asthma, severe respiratory failure (efficacy and safety not studied).
- with a violation of liver function;
- in case of impaired renal function;
- in elderly patients.
PREGNANCY AND LACTATION
In connection with the lack of necessary clinical data, the use of the drug Refralon is not recommended for pregnancy.
Information on the allocation of the drug in breast milk is not available. If it is necessary to prescribe the drug during lactation, breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution in the violation of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution in the violation of liver function.
APPLICATION FOR CHILDREN
Contraindicated up to 18 years.
APPLICATION IN ELDERLY PATIENTS
With caution in elderly patients.
Introduction of the drug Refralon should be performed in the intensive care unit with the subsequent stay in it for continuous monitoring of the ECG in order to timely identify possible ventricular arrhythmias and dynamic measurement of the QT interval, QTc until normalization of these parameters or up to 24 hours. Before each administration and after the administration of each of the consecutive doses of the preparation, it is necessary to record the ECG in 12 leads to monitor the heart rate, the duration of the intervals QRS, QT, QTc.
It should be taken into account that in elderly patients, patients with impaired renal and / or liver function, the risk of side effects and the likelihood of drug overdose is higher.
Impact on the ability to drive vehicles and other mechanisms
Information on the effect of the drug on the ability to drive vehicles and on the performance of other potentially hazardous activities requiring increased attention and speed of psychomotor reactions are lacking.
Symptoms: severe bradycardia is possible (heart rate less than 50 beats / min), an increase in the duration of the QT interval> 500 ms, the occurrence of ventricular arrhythmias. The incidence of polymorphic ventricular tachycardia of the pirouette type is 1.5%.
Treatment: when a stable paroxysm of ventricular tachycardia of the "pirouette" type is recommended, intravenous magnesium salts or more frequent cardiac stimulation, if necessary - electrical cardioversion. With the development of severe bradycardia against the background of the restoration of sinus rhythm, the administration of atropine is possible.
There is no specific antidote.
Contraindicated combination of the drug Refralone with drugs potentially capable of causing polymorphic ventricular tachycardia such as "pirouette", including:
- antiarrhythmics: 1A class (quinidine, hydroquinidine, disopyramide, procainamide), grade III (dofetilide, amiodarone, dronedarone, ibutilide, brethilia tosylate), sotalol;
- other (not anti-arrhythmic) drugs, such as bepridil, vinamine; some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiaprid, verialapride), butyrophenones (droperidol, haloperidol), sertindole, pimozide;tricyclic antidepressants; cisapride; macrolide antibiotics (erythromycin for intravenous administration, spiramycin); azoles; antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine); pentamidine with parenteral administration; diphenamyl methyl sulfate; misolastine; astemizole; terfenadine; fluoroquinolones (eg, moxifloxacin);
Because of the risk of developing bradycardia and conduction disorders, it is not recommended to administer the drug on the background of taking beta-adrenoblockers, blockers of "slow" calcium channels, pacing heart rate (verapamil, diltiazem), digoxin.
TERMS OF RELEASE FROM PHARMACY
Leave only for cardiological departments of medical and preventive institutions.
TERMS AND CONDITIONS OF STORAGE
In a dry, protected from light place at a temperature of no higher than 25 В° C. Keep out of the reach of children. Shelf life - 2 years.
The information is provided for your information, do not self-medicate, it is dangerous for your health.