Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Antiarrhythmic agent of class IC, blocker of sodium channels. Reduces the maximum depolarization rate of phase 0 of the action potential and its amplitude mainly in Purkinje fibers and contractile fibers of the ventricles, lowers the automatism. Highly effective in ventricular arrhythmias; with supraventricular rhythm disorders, the efficiency is somewhat lower. Propaphenone has a weakly expressed beta-adrenoblocking effect.
PHARMACOKINETICS
Pharmacokinetics of propafenone is characterized by significant individual differences.
After ingestion, the absorption is rapid and almost complete - more than 90%, C max in blood plasma is reached after 1-3.5 hours. Binding to proteins is 97%. It is subjected to intensive metabolism during the "first passage" through the liver with the formation of 2 active metabolites - 5-hydroxypropaphenone and N-despropylpropaphenone, which have antiarrhythmic activity comparable to propafenone, but are present in concentrations of 20% of the concentrations of propafenone.
T 1/2 in patients with intensive metabolism (more than 90% of cases) - 2-10 hours, with a slow metabolism (less than 10% of cases) - 10-32 hours. It is excreted by the kidneys - 38% in the form of metabolites, 1% - in unchanged form; through the intestine - 53% in the form of metabolites.
INDICATIONS
Treatment and prevention of supraventricular and ventricular extrasystoles, paroxysmal rhythm disorders (supraventricular tachycardia, including with WPW syndrome, ventricular tachycardia).
DOSING MODE
If administered orally, the initial dose is 450-600 mg / day, if necessary, increase the dose to 900 mg / day.
With IV injection, the initial dose is 500 Ојg / kg, if necessary, the dose is increased to 1-2 mg / kg.
SIDE EFFECT
From the side of the cardiovascular system: bradycardia, slowing of sinoatrial, AV and intraventricular conduction, reduction of myocardial contractility (in predisposed patients), arrhythmogenic effect; when taking in high doses - orthostatic hypotension.
On the part of the digestive system: when taken in high doses, nausea, anorexia, a feeling of heaviness in the epigastrium, constipation are possible; rarely - violations of the liver.
From the side of the central nervous system: when taking in high doses - headache, dizziness; rarely - visual impairment.
On the part of the hematopoiesis system: leukopenia, agranulocytosis, thrombocytopenia.
On the part of the reproductive system: oligospermia.
Allergic reactions: rarely - skin rash.
CONTRAINDICATIONS
Severe forms of chronic heart failure, severe arterial hypotension, cardiogenic shock, pronounced bradycardia, SSSU, AV blockade of II and III degree, electrolyte imbalance, myasthenia gravis, severe obstructive pulmonary diseases, hepatic cholestasis, childhood, hypersensitivity to propafenone.
PREGNANCY AND LACTATION
Use in pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.
If it is necessary to use during the lactation period, the question of stopping breastfeeding should be solved.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution apply for severe impairment of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution for violations of liver function.
APPLICATION FOR CHILDREN
Contraindicated in childhood.
APPLICATION IN ELDERLY PATIENTS
In elderly patients, propafenone is used in lower doses.
SPECIAL INSTRUCTIONS
They are used with caution in cases of violations of liver function, severe renal dysfunction, as well as in combination with other antiarrhythmics with similar electrophysiological parameters.
Treatment should be started in a hospital, because the risk of arrhythmogenic action associated with the use of propafenone is increased. It is recommended that the previous antiarrhythmic therapy should be discontinued before the treatment with propafenone begins at a time equal to 2-5 T 1/2 .
Propaphenone is characterized by pronounced individual differences in the concentration of active substance in the blood plasma, therefore, careful selection of doses for each patient is recommended.
Intravenous administration should be carried out under the constant control of blood pressure, heart rate and ECG. If during the course treatment or against the background of intravenous administration QRS or QT interval broadening is noted more than 20%, compared with the initial values, the dose should be reduced or propafenone should be temporarily discontinued. In elderly patients, patients with a body weight of less than 70 kg, propafenone is used in lower doses.
Impact on the ability to drive vehicles and manage mechanisms
They are used with caution in patients engaged in potentially dangerous activities requiring increased attention and speed of psychomotor reactions.
DRUG INTERACTION
With simultaneous use with anticholinergics, anticholinergic action may be enhanced.
With simultaneous use with anticholinesterase agents (including with pyridostigmine), the effectiveness of pyridostigmine decreases with myasthenia gravis.
When used simultaneously with beta-adrenoblockers, tricyclic antidepressants, local anesthetics, the antiarrhythmic effect of propafenone in ventricular arrhythmias may be increased.
With the simultaneous use of propafenone can potentiate the effect of indirect anticoagulants.
With simultaneous application with phenobarbital, the excretion of propafenone from the body increases and its concentration in the blood plasma decreases. It is believed that other barbiturates react with propafenone in the same way.
At simultaneous application with ketoconazole the case of development of cramps is described.
With simultaneous use, it is possible to increase plasma concentrations of propranolol, metoprolol, cyclosporin, digoxin.
With simultaneous use with rifampicin, the concentration of propafenone in the blood plasma decreases and its therapeutic effectiveness is significantly reduced. This is due to the fact that rifampicin induces isoenzymes CYP3A4 / 1A2 and phase II glucuronization of propafenone. Rifampicin does not affect the metabolism of propafenone, due to the activity of the isoenzyme CYP2D6.
With simultaneous application, cases of increasing the concentration of theophylline in the blood plasma and the development of toxic reactions are described.
Quinidine inhibits the metabolism of propafenone in the liver in individuals with a high level of metabolism, which leads to a significant increase in its concentration in the blood plasma. In this case, the effectiveness of propafenone does not change, because the production of its active metabolite (5-hydroxypropaphenone) simultaneously decreases by a factor of 2.
Quinidine increases the beta-blocking effects of propafenone in individuals with a high level of metabolism in the liver, only the initial active substance, and not metabolites, has beta-blocking activity.
With simultaneous use with cimetidine, a slight increase in the concentration of propaphenone in the blood plasma and the expansion of the QRS complex on the ECG are possible.
With the simultaneous use of erythromycin can inhibit the metabolism of propafenone.
