Composition, form of production and packaging
The tablets covered with a cover of white or almost white color, round, biconcave.
1 tab.
propafenone hydrochloride 150 mg,
which corresponds to the content of propafenone 135.7 mg
Excipients: microcrystalline granulated cellulose, corn starch, copovidone, croscarmellose sodium, magnesium stearate, sodium lauryl sulfate, hypromellose 5, macrogol 6000, titanium dioxide, emetic dimethicone with silicon dioxide.
10 pieces. - blisters (5) - packs of cardboard.
The tablets covered with a cover of white or almost white color, round, biconcave.
1 tab.
propafenone hydrochloride 300 mg,
which corresponds to the content of propafenone 271.05 mg
Excipients: microcrystalline granulated cellulose, corn starch, copovidone, croscarmellose sodium, magnesium stearate, sodium lauryl sulfate, hypromellose 5, macrogol 6000, titanium dioxide, emetic dimethicone with silicon dioxide.
10 pieces. - blisters (5) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Antiarrhythmic drug class IC, blocks fast sodium channels. Has a weak? -adrenoblocking activity (corresponding to approximately 1/40 of the propranolol activity) and m-holinoblocking effect. Antiarrhythmic effect is based on local anesthetic and direct membrane-stabilizing action on myocardiocytes, as well as blockade of adrenergic ОІ-adrenoreceptors and calcium channels.
Local anesthetic effect approximately corresponds to the activity of procaine.
Propaphenone, blocking the fast sodium channels, causes a dose-dependent decrease in the rate of depolarization and inhibits the phase 0 of the action potential and its amplitude in Purkinje fibers and contractile fibers of the ventricles, inhibits automatism. Slows down the Purkinje fibers. Lengthens the time spent on the sinoatrial node and atria. When using propafenone, the PQ interval is extended and the QRS complex (from 15 to 25) is expanded on the ECG, as well as the AH and HV intervals on the histogram. Slowing down the drug, the drug lengthens the effective refractory period in the atria, AV-node, additional beams, and, to a lesser extent, ventricles. There are no significant changes in the QT interval. Electrophysiological effects are more pronounced in ischemic than in normal myocardium. Has a negative inotropic effect, which usually manifests itself when the left ventricular ejection fraction is lower than 40%.
The effect of the drug begins 1 hour after ingestion, reaches a maximum after 2-3 hours and lasts 8-12 hours.
PHARMACOKINETICS
Suction
After taking the drug, more than 95% of the propafenone is absorbed. Bioavailability of the drug increases non-linearly with increasing dose (from 5% to 12% with a single dose increase from 150 mg to 300 mg, and when taken in a dose of 450 mg - up to 40-50%). C max is achieved in 1-3.5 hours and is 500-1500 Ојg / l.
Distribution
Binding to blood plasma proteins and internal organs is 85-97%.
Permeability through the BBB and the placental barrier is low. V d - 3-4 l / kg.
Metabolism
Propafenone is almost completely metabolized. 11 metabolites of the preparation are described, pharmacologically active are 5-hydroxypropaphenone and N-depropylpropaphenone, which have comparable to propafenone antiarrhythmic activity. Oxidative metabolism depends on specific cytochrome, the activity of which is genetically determined.
The therapeutic range of the concentration of propafenone in the blood plasma is 0.5-2 mg / l.
Excretion
T 1/2 in patients with intensive metabolism is from 2 to 10 hours, in patients with delayed metabolism - from 10 to 32 hours.
It is excreted in the urine - 38% in the form of metabolites (<1% unchanged), with bile - 53% (in the form of glucuronides and sulfates).
Pharmacokinetics in special clinical cases
With hepatic failure, excretion decreases.
INDICATIONS
- prevention and treatment of supraventricular and ventricular extrasystoles;
- prevention and treatment of paroxysmal rhythm disturbances (supraventricular - atrial fibrillation and flutter, Wolff-Parkinson-White syndrome);
- prevention and treatment of atrial-ventricular re-entry of tachycardia;
- prevention of stable monomorphic ventricular tachycardia.
DOSING MODE
The dosage regimen is set individually and adjusted by the doctor.
The drug is taken after a meal. Tablets should be swallowed whole, not liquid, squeezed with a small amount of water.
The drug is prescribed for 150 mg 3 times / day (every 8 hours). The daily dose is 450 mg.
The dose is increased gradually (every 3-4 days) to 600 mg / day (divided into 2 doses) or up to 900 mg / day (divided into 3 doses).
If, on the background of treatment, the QRS or QT interval is extended by more than 20% compared to the baseline values, or the PQ interval is extended by more than 50%, the QT interval is extended by more than 500 msec, the frequency and severity of the arrhythmia increase, the dose or temporarily interrupt the use of Propanorm В® .
In patients older than 70 years, as well as in patients with a body weight <70 kg, smaller doses are used (the first dose is given in a hospital under ECG and blood pressure control).
If liver function is impaired (cumulation possible) Propanorm В® is used in doses of 20-30% of the usual.
If the renal function is impaired (CC <10 ml / min), the initial dose is 50% of the initial dose.
SIDE EFFECT
From the cardiovascular system: bradycardia, AV dissociation, ventricular tachyarrhythmias, angina pectoris, worsening of the course of heart failure (in patients with decreased left ventricular function), sinoatrial blockade, AV blockade, intraventricular conduction disorders, supraventricular tachyarrhythmias, when taken in high doses - orthostatic hypotension.
On the part of the digestive system: a change in taste, dry mouth, bitterness in the mouth, nausea, decreased appetite, a feeling of heaviness in the epigastrium, constipation or diarrhea; rarely - violations of the liver, cholestatic jaundice, cholestasis.
From the side of the central nervous system: headache, dizziness; rarely - blurred vision, diplopia, convulsions.
From the hemopoietic system: leukopenia, agranulocytosis, increased bleeding time, thrombocytopenia, the appearance of antinuclear antibodies.
On the part of the reproductive system: oligospermia, decreased potency.
Allergic reactions: skin rash, itching, exanthema, reddening of the skin, urticaria, lupus-like syndrome.
Other: weakness, bronchospasm, hemorrhagic rashes on the skin.
CONTRAINDICATIONS
- severe forms of chronic heart failure (in the stage of decompensation), uncontrolled chronic heart failure;
- cardiogenic shock (with the exception of arterial hypotension due to tachycardia and antiarrhythmic shock);
- pronounced bradycardia;
- severe arterial hypotension;
- Sinoatrial blockade, violation of intracirculation;
- blockade of the legs of the bundle;
- intraventricular bifascicular blockade and AV blockade of II and III degree (without cardiac pacemaker);
- SSSU;
- syndrome of "tachycardia-bradycardia";
- myocardial infarction;
- the period of lactation (breastfeeding);
- children and adolescents under 18 years of age (efficacy and safety not established);
- intoxication with digoxin;
- Hypersensitivity to the components of the drug.
Caution should be given to the drug when COPD, myasthenia gravis (myasthenia gravis), heart failure (ejection fraction less than 30%), cardiomyopathy, arterial hypotension, hepatic cholestasis, hepatic and / or renal insufficiency, electrolyte disorders (must be corrected before propafenone administration), patients at the age of over 70 years, patients with a permanent or temporary pacemaker, with the simultaneous appointment with other antiarrhythmics of a similar effect on the electrophysiology of the heart.
PREGNANCY AND LACTATION
The use of propafenone during pregnancy, especially in the first trimester, is only possible if the expected benefit to the mother exceeds the potential risk to the fetus.
APPLICATION FOR FUNCTIONS OF THE LIVER
If the renal function is impaired (CC <10 ml / min), the initial dose is 50% of the initial dose.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
If liver function is impaired (cumulation possible) Propanorm is used in doses of 20-30% of normal.
APPLICATION FOR CHILDREN
Contraindication: children and adolescents under 18 years of age (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
In patients older than 70 years, as well as in patients with a body weight <70 kg, smaller doses are used (the first dose is given in a hospital under ECG and blood pressure control).
SPECIAL INSTRUCTIONS
During the course of treatment, especially at the beginning of therapy, ECG monitoring is necessary.
Treatment is recommended to begin in a hospital, because the risk of arrhythmogenic action associated with the use of propafenone is increased.
Propanorm В® should be used under the control of electrolyte balance of blood (especially potassium concentration) and ECG; Periodically it is necessary to determine the activity of hepatic transaminases.
In the treatment of ventricular arrhythmias, propafenone is more effective than antiarrhythmic drugs IA and IB classes.
In patients with insufficient liver function, the bioavailability of propafenone increases by 70%, in such patients it is recommended to reduce the dose and to conduct regular monitoring of laboratory parameters.
Indication and dose should be carefully determined for patients with an established pacemaker.
It is necessary to conduct clinical and laboratory monitoring of patients undergoing long-term treatment with anticoagulants and hypoglycemic drugs, while using the preparation PropanormВ®.
In the event that in the treatment of sinoatrial blockade or AV-blockade of the third degree, or a frequent recurrence of the extrasystole, treatment should be interrupted.
Given the possibility of proaritmogenic exposure, the drug is recommended to be used only for the intended purpose and under the supervision of a doctor.
Impact on the ability to drive vehicles or manage machinery
During the treatment period it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
At a single-dose dose, 2 times the daily dose, the symptoms of intoxication can appear after 1 hour, a maximum after a few hours.
Symptoms: persistent decrease in blood pressure, nausea, dry mouth, vomiting, mydriasis, drowsiness, extrapyramidal disorders, confusion, bradycardia, QT interval prolongation, atrial and intraventricular conduction abnormalities, ventricular tachyarrhythmias, paroxysms of polymorphic ventricular tachycardia, sinoatrial blockade, AV blockade , asystole, coma, convulsions, delirium, pulmonary edema.
Treatment: gastric lavage, defibrillation, administration of dobutamine, diazepam; if necessary, ventilation and indirect cardiac massage. Hemodialysis is ineffective.
DRUG INTERACTION
Do not combine Propanorm В® with lidocaine, t. cardiodespressive effect is intensified.
With simultaneous use, propafenone increases the concentration of propranolol, metoprolol, digoxin (increases the risk of developing glycoside intoxication), anticoagulants of indirect action, cyclosporine in blood plasma.
With the simultaneous use of propafenone enhances the effect of warfarin (by blocking the metabolism).
At simultaneous application with beta-adrenoblockers, tricyclic antidepressants, an antiarrhythmic effect is possible.
When used simultaneously with local anesthetics, the risk of CNS damage increases.
Cimetidine and quinidine, slowing metabolism, increase the concentration of propafenone in plasma by 20%, rifampicin - reduces.
With simultaneous application with propafenone, amiodarone increases the risk of developing pirouette tachycardia.
Drugs that inhibit the sinoatrial node and AV node and have a negative inotropic effect, while simultaneous application with propafenone increase the risk of side effects.
Drugs that inhibit bone marrow hematopoiesis, when used simultaneously with propafenone, increase the risk of myelosuppression.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of reach of children, dry, protected from light at a temperature of 15-25 В° C. Shelf life - 3 years.
