Propafenone 150 mg 50 pcs. film-coated tablets

Pharmacological properties of the drug Propafenone

A highly active class I antiarrhythmic drug (according to the Williams classification) with a moderate blocking effect on β-adrenergic receptors. Reduces the maximum depolarization rate and action potential amplitude in Purkinje fibers. Has no effect on resting potential. Effective for ventricular extrasystole, for supraventricular rhythm disturbances, especially paroxysms of atrial fibrillation/flutter. Clinically significant suppression of ventricular tachycardia is observed in at least 50% of patients receiving propafenone. They are also used to relieve and prevent attacks of tachycardia caused by conduction disturbances in the AV node and with WPW syndrome. Propafenone provides a lasting therapeutic effect in 80% of patients with this pathology. Propafenone has been proven effective in treating organic heart lesions, including in patients who have suffered a myocardial infarction. Recommended for resistance to other antiarrhythmic drugs. At doses of 450–1200 mg/day, it eliminates arrhythmia in more than half of these patients. The maximum content in blood plasma is achieved 2–3 hours after oral administration.

Propafenone 3.5 mg/ml 10 ml 10 pcs. injection

pharmachologic effect

The effect is based on a local anesthetic and direct membrane-stabilizing effect on myocardiocytes. It has m-anticholinergic and beta-adrenergic blocking (weak) effects, blocks sodium channels.

Composition and release form Propafenone 3.5 mg/ml 10 ml 10 pcs. injection

film-coated tablets - 1 tablet. propafenone hydrochloride - 150 mg excipients: lactose monohydrate; MCC; sodium lauryl sulfate; sodium starch glycolate; povidone; talc; magnesium stearate; opadry white Y-1-7000. in a dark glass bottle 40 pcs.; 1 bottle in a cardboard pack.

Description of the dosage form

White, round, biconvex, film-coated tablets, scored on one side.

Directions for use and doses

For the treatment and prevention of extrasystole, it is prescribed orally at an initial dose of 450-600 mg per day. If the effect is insufficient, the dose is increased to 900 mg. The tablets should be taken after meals, without chewing, with a small amount of liquid. For paroxysmal rhythm disturbances, it is prescribed intravenously by drip at an initial dose of 500 mcg per kg of body weight, if the effect is insufficient - 1-2 mg/kg.

Pharmacodynamics

Class IC antiarrhythmic drug. Blocks fast sodium channels, causes a dose-dependent decrease in the rate of depolarization, inhibits phase 0 of the action potential, its amplitude in Purkinje fibers and contractile fibers of the ventricles, and inhibits automaticity. Extends conduction time through the sinoatrial node (SA) and atria, slows down conduction through Purkinje fibers. Causes prolongation of the PQ interval and expansion of the QRS complex, as well as the AH and HV intervals. By slowing down conduction, it lengthens the effective refractory period in the atria, in the AV node, in accessory bundles and, to a lesser extent, in the ventricles. The QT interval does not change significantly. Electrophysiological effects are more pronounced in ischemic compared with normal myocardium. The local anesthetic effect approximately corresponds to the activity of procaine. Beta-blocking activity corresponds to approximately 1/40 of the activity of propranolol. It has a negative inotropic effect, which usually occurs when the left ventricular ejection fraction decreases below 40%. The action begins 30 minutes after oral administration, reaches a maximum after 2–3 hours and lasts 8–12 hours.

Pharmacokinetics

After oral administration, absorption is more than 95%. Bioavailability increases nonlinearly with increasing dose: when increasing a single dose from 150 to 300 mg, it increases from 5 to 12%, and up to 450 mg, to 40-50%. Cmax fluctuates in the range of 500-1500 µg/l, Tmax - 2-3 hours. Passage through the BBB and the placental barrier is insignificant. Distribution volume - 3-4 l. Communication with proteins of plasma and internal organs (liver, lungs, etc.) - 85-97%. Metabolized almost completely. 11 metabolites of the drug have been described, of which the metabolically active ones are 5-hydroxypropafenone and N-depropylpropafenone, which have antiarrhythmic activity comparable to propafenone. Oxidative metabolism depends on a specific cytochrome, whose activity is genetically determined. The therapeutic range of plasma concentration is 0.5-2.0 mg/l. T1/2 in persons with fast metabolism is 2-10 hours, slow - 10-32 hours, biological T1/2 - 6.2 hours. Excreted by the kidneys.

Indications for use Propafenone 3.5 mg/ml 10 ml 10 pcs. injection

• supraventricular and ventricular extrasystoles;
• supraventricular tachycardia, ventricular tachycardia.

Contraindications

• severe forms of chronic heart failure;
• electrolyte imbalance;
• myasthenia gravis;
• bronchial asthma;
• hypersensitivity to the drug.

Application Propafenone 3.5 mg/ml 10 ml 10 pcs. solution for injection during pregnancy and lactation

Contraindicated during pregnancy, breastfeeding and childhood.

special instructions

Treatment, especially the beginning of the course, must be carried out under constant monitoring of ECG and blood electrolyte balance (especially potassium concentration). It is necessary to start taking the drug in a hospital setting, due to the increased risk of proarrhythmogenic effects. The activity of “liver” transaminases should be periodically determined. In patients with insufficient liver function, bioavailability increases by 70% (cumulation is possible), so it is recommended to reduce the dose and regularly monitor laboratory parameters. In patients with a pacemaker, the dose must be determined with extreme caution. Patients taking anticoagulants and hypoglycemic drugs for a long time require careful clinical and laboratory monitoring. If SA or AV block of the third degree or frequently repeated extrasystole appears during therapy, treatment must be interrupted. It is recommended to use the drug only as directed and under the supervision of a physician, given its likely proarrhythmogenic effect. During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: persistent decrease in blood pressure, nausea, dry mouth, vomiting, mydriasis, drowsiness, extrapyramidal disorders, confusion, bradycardia, prolongation of the QT interval, impaired intraatrial and intraventricular conduction, SA and AV blockade, ventricular tachyarrhythmias, paroxysms of polymorphic ventricular tachycardia, asystole , coma, convulsions, delirium, pulmonary edema (symptoms of intoxication can occur with a single dose of 2 times the daily dose, and appear after an hour, a maximum of several hours). Treatment: gastric lavage, defibrillation, administration of dobutamine, diazepam; if necessary, mechanical ventilation and indirect cardiac massage. Hemodialysis is ineffective.

Side effects Propafenone 3.5 mg/ml 10 ml 10 pcs. injection

• nausea, feeling of heaviness in the stomach, constipation;
• headache, dizziness;
• skin rashes;
• liver dysfunction;
• blood picture disturbance;
• decrease in sperm count.

Drug interactions

Combination with lidocaine is contraindicated (the cardiodepressive effect increases). Increases the plasma concentration of propranolol, indirect anticoagulants, cyclosporine. Enhances the effect of warfarin (blocks metabolism). When used simultaneously with beta-blockers and tricyclic antidepressants, the antiarrhythmic effect may be enhanced; with local anesthetics, the risk of central nervous system damage may increase. Cimetidine and quinidine, by slowing metabolism, increase the concentration of propafenone in plasma by 20%, rifampicin decreases it. Amiodarone increases the risk of developing pirouette tachycardia. Drugs that suppress the SA and AV nodes and have a negative inotropic effect increase the risk of side effects. Drugs that inhibit bone marrow hematopoiesis increase the risk of myelosuppression.

Use of the drug Propafenone

Individual dose selection is carried out under the control of ECG and blood pressure. QRS and the QT increases by more than 20%, it is necessary to reduce the dose or temporarily discontinue propafenone until the ECG values ​​normalize. The therapeutic dose for patients weighing 70 kg is usually 450–600 mg/day (150 mg 3 times a day or 300 mg 2 times a day). In some cases, it can be increased to 900 mg (300 mg 3 times a day). As an exception, it can be prescribed at a higher dose under strict ECG monitoring. Patients with lower body weight should reduce doses accordingly. In elderly patients and patients with severe myocardial damage at the beginning of treatment, the dose should be increased gradually.

Propafenone 150 mg 50 pcs. film-coated tablets

pharmachologic effect

Antiarrhythmic drug.

Composition and release form Propafenone 150 mg 50 pcs. film-coated tablets

Tablets - 1 tablet:

• active substance: propafenone hydrochloride 150,000 mg;
• excipients: lactose monohydrate 10.120 mg, sodium lauryl sulfate 2.300 mg, sodium carboxymethyl starch 18.400 mg, magnesium stearate 0.690 mg, povidone 11.500 mg, talc 0.460 mg, microcrystalline cellulose 36.530 mg;
• Shell: opadry white Y-1-7000 5,000 mg (hypromellose 5cP 3.125 mg, titanium dioxide E171 1.5625 mg, macrogol-400 0.3125 mg).

10 tablets in a perforated blister made of aluminum foil and PVC film.

4 blisters (40 tablets) or 5 blisters (50 tablets) along with instructions for use are placed in a cardboard box.

Description of the dosage form

Round, biconvex, white film-coated tablets with a score line on one side. The kernel is white.

Directions for use and doses

Inside. The tablets should be swallowed whole after meals with a small amount of water.

The dosage regimen is set individually and adjusted by the doctor. It is recommended to begin therapy in a hospital, having first discontinued all antiarrhythmic drugs (under the control of blood pressure, ECG, assessment of the width of the QRS complex).

In patients with a significantly widened QRS complex and AV block of II and III degrees, it is recommended to reduce the dose.

If the patient's body weight is 70 kg or more, the initial dose is 150 mg 3 times a day (in the hospital under blood pressure and ECG monitoring). The dose can be increased gradually, at intervals of 3-4 days, up to 300 mg 2 times a day, and if necessary, up to a maximum dose of 300 mg 3 times a day.

In elderly patients, patients weighing less than 70 kg, the use of the drug begins with lower doses, gradually increasing the dose. The same tactics should be followed during maintenance therapy. You should not start increasing the dose of the drug if the duration of use of the drug is less than 5-8 days.

In case of impaired liver function (cumulation is possible), Propafenone is used in doses of 20-30% of the usual; in case of impaired renal function (creatinine clearance less than 10%), the initial dose is 50% of the usual.

Pharmacodynamics

Propafenone is an antiarrhythmic drug with membrane-stabilizing properties, sodium channel blocker properties (class IC) and weak beta-blocking activity (class II).

The local anesthetic effect approximately corresponds to the activity of procaine. Reduces the maximum depolarization rate of phase 0 of the action potential and its amplitude in Purkinje fibers and contractile fibers of the ventricles, inhibits automaticity. Slows down conduction along Purkinje fibers. Prolongs conduction time through the sinoatrial (SA) node and atria. Does not affect or slightly increase the adjusted time to recovery of sinus node function with programmed electrical stimulation.

Increases the effective refractory period of the atrioventricular node, inhibits conduction along additional pathways in the retrograde and antegrade directions, and increases the threshold for ventricular stimulation.

Electrophysiological effects are more pronounced in ischemic than in normal myocardium. It has a negative inotropic effect, which usually manifests itself when the left ventricular ejection fraction decreases below 40%. The effect begins 1 hour after ingestion and lasts for 8-12 hours.

Pharmacokinetics

Absorption

More than 95% of the drug is absorbed. Systemic bioavailability is 5-50%. Taken with food increases bioavailability in patients with extensive metabolism.

Propafenone exhibits dose-dependent bioavailability, which increases nonlinearly with increasing dose: it increases from 5% to 12% when increasing a single dose from 150 mg to 300 mg, and at 450 mg - to 40-50%. The time to reach maximum plasma concentration (TCmax) after oral administration is 1-3.5 hours and its value ranges from 500 to 1500 mcg/l. Equilibrium concentration (Css) in blood plasma is achieved 3-4 days after the start of therapy.

Distribution

Permeability through the blood-brain and placental barrier is low. The concentration of propafenone in the umbilical cord is 30% of its concentration in the mother's blood. Volume of distribution - 3-4 l/kg.

Communication with proteins of blood plasma and internal organs (liver, lungs, etc.) - 85-97%. Propafenone undergoes significant and saturated presystemic biotransformation by the CYP2D6 isoenzyme (the “first pass” effect through the liver), which leads to absolute bioavailability, dependent on the dose and dosage form of the drug.

Metabolism

There are 2 models of genetically determined metabolism of propafenone. In more than 90% of patients, propafenone is rapidly and significantly metabolized, the half-life (T1/2) ranges from 2.8 to 11 hours.

11 metabolites of propafenone have been described, two of them are pharmacologically active: 5-hydroxypropafenone is formed using the CYP2D6 isoenzyme, and N-depropylpropafenone (norpropafenone) - using the CYP3A4 and CYP1A2 isoenzymes. In less than 10% of patients, propafenone is metabolized more slowly because 5-hydroxypropafenone is not formed or is formed in small quantities. With this type of metabolism, the half-life is about 17 hours. With significant metabolism with a saturable hydroxylation cycle using the CYP2D6 isoenzyme, the pharmacokinetics of propafenone are non-linear, and with slow metabolism - linear. Since the equilibrium state of pharmacokinetic parameters is achieved 3-4 days after taking the drug orally in all patients, the dosage regimen of the drug is the same for all patients, regardless of metabolic rate. Pharmacokinetics has significant individual variability, which is mainly due to the effect of “first pass” through the liver, as well as its nonlinearity during extensive metabolism. Variability in the concentration of propafenone in the blood requires careful titration of the dose and monitoring of patients, including ECG monitoring.

Removal

Excreted by the kidneys - 38% in the form of metabolites (less than 1% unchanged), through the intestines with bile - 53% (in the form of glucuronides and sulfates of metabolites and unchanged propafenone. With liver failure, excretion is reduced.

Indications for use Propafenone 150 mg 50 pcs. film-coated tablets

Prevention and treatment of ventricular arrhythmias.

Prevention and treatment of paroxysmal supraventricular tachyarrhythmias (including atrial fibrillation/flutter; paroxysmal supraventricular tachycardia of the re-entry type involving the atrioventricular node or additional conduction pathways, when other therapy is ineffective or contraindicated).

Contraindications

If you have one of the listed diseases, be sure to consult your doctor before taking the drug.

• Hypersensitivity to propafenone and the components of the drug;
• severe forms of chronic heart failure (in the stage of decompensation), uncontrolled chronic heart failure;
• cardiogenic shock (with the exception of arterial hypotension caused by tachycardia and antiarrhythmic shock);
• severe bradycardia and arterial hypotension;
• sinoatrial blockade, intraatrial conduction disorders;
• bundle branch block or distal block (in patients without a pacemaker);
• severe disturbances in water and electrolyte balance (for example, disturbances in potassium metabolism), myasthenia gravis;
• severe forms of chronic obstructive pulmonary disease (COPD), bronchospasm (history);
• intraventricular bifascicular block and atrioventricular block of II-III degree (without pacemaker);
• sick sinus syndrome;
• “tachycardia-bradycardia” syndrome;
• pronounced organic changes in the myocardium, such as refractory chronic heart failure with a left ventricular ejection fraction of less than 35% and cardiogenic shock, with the exception of arrhythmic shock;
• simultaneous use of ritonavir at a dose of 800-1200 mg/day;
• patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• age under 18 years (efficacy and safety have not been established).

Carefully:

If you have one of the listed diseases, be sure to consult your doctor before taking the drug.

Myasthenia gravis, impaired renal and/or liver function, COPD (with extreme caution due to beta-blocking action), elderly age, patients with an installed artificial cardiac pacemaker, fluid and electrolyte imbalance, arterial hypotension, simultaneous use with other antiarrhythmics means.

Application Propafenone 150 mg 50 pcs. film-coated tablets during pregnancy and breastfeeding

The use of propafenone during pregnancy, especially in the first trimester, is possible only when the expected benefit to the mother outweighs the potential risk to the fetus. Propafenone penetrates the placental barrier. The concentration of propafenone in the umbilical cord is 30% of its concentration in the mother's blood.

Propafenone is excreted into breast milk. If it is necessary to use the drug propafenone during lactation, breastfeeding should be stopped.

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 setting, since the risk of arrhythmogenic effects associated with the use of Propafenone is increased.

The use of Propafenone should be carried out under the control of blood electrolyte balance (especially potassium content) and ECG. In case of ECG changes, for example, widening of the QRS complex or prolongation of the QT interval by more than 25% or PR interval by more than 50% or the QT interval by more than 500 ms or an increase in the frequency and severity of cardiac arrhythmias, it is necessary to decide whether to continue treatment.

In elderly patients or patients with significant impairment of left ventricular function (left ventricular ejection fraction

In elderly patients or patients with organic changes in the myocardium, the dose of the drug should be titrated with great caution. When treating paroxysmal atrial fibrillation, a transition from atrial fibrillation to atrial flutter with 2:1 or 1:1 ventricular conduction, with a very high ventricular rate (ie, >180 beats per minute), may occur.

Treatment with the drug may affect the sensitivity threshold and frequency threshold of artificial pacemakers. Therefore, pacemakers must be checked and, if necessary, reprogrammed, since the drug may affect the sensitivity threshold and frequency threshold of the artificial pacemaker. The activity of “liver” transaminases should be periodically determined.

In the treatment of ventricular arrhythmias, Propafenone is more effective than class IA and IB antiarrhythmic drugs.

In patients with insufficient liver function, the bioavailability of Propafenone increases by 70%; in such patients it is recommended to reduce the dose and regularly monitor laboratory parameters.

Indications and dose must be determined especially carefully for patients with an artificial pacemaker.

Patients undergoing long-term treatment with anticoagulants and hypoglycemic drugs should be closely monitored both clinically and laboratory.

If, during therapy, sinoatrial block or third degree atrioventricular block, or frequently recurring extrasystoles appear, then treatment must be stopped.

Considering the likely proarrhythmogenic effect on the patient's prognosis, the drug is recommended to be used only as directed and under the supervision of a physician.

The drug contains lactose monohydrate. It is necessary to take into account in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Features of the action of the drug upon its withdrawal

Despite the absence of BMCC (slow calcium channel blocker) syndrome of “hepatic” transaminases.

If any of the side effects indicated in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Drug interactions

Pharmacodynamic interaction

When lidocaine is administered intravenously simultaneously with propafenone, the risk of damage to the central nervous system increases.

When used simultaneously with beta-blockers, the antiarrhythmic effect may be enhanced; with local anesthetics and drugs that inhibit cardiac activity, the effect of propafenone may be enhanced. When propafenone is used simultaneously with mizolastine, ritonavir, tricyclic antidepressants or antipsychotics, the risk of developing arrhythmias increases.

The use of propafenone in combination with phenobarbital and/or rifampicin may reduce the antiarrhythmic effectiveness of propafenone hydrochloride.

Amiodarone increases the risk of developing pirouette tachycardia. Doses of both drugs may need to be adjusted based on therapeutic response. Drugs that suppress the sinoatrial and atrioventricular nodes and have a negative inotropic effect increase the risk of side effects. Medicines that inhibit bone marrow hematopoiesis increase the risk of myelosuppression.

Pharmacokinetic interaction

Increases the plasma concentration of propranolol, metoprolol, digoxin (the risk of developing glycoside intoxication increases), indirect anticoagulants, cyclosporine, theophylline, desipramine. Enhances the effect of warfarin (blocks metabolism).

Cimetidine, quinidine, ketoconazole, tropisetron, dolasetron, mizolastine, erythromycin and grapefruit juice, slowing metabolism, increase the plasma concentration of propafenone by 20%, so patients should be carefully monitored and the dose of propafenone adjusted accordingly; rifampicin reduces it.

Use of propafenone hydrochloride in combination with venflaxin may result in increased venflaxin concentrations. With the simultaneous use of propafenone hydrochloride and fluoxetine in “fast” metabolizers, the Cmax of S-propafenone increases by 39% and AUC by 50%, and the Cmax of R-propafenone by 71% and AUC by 50%. Therefore, lower doses of propafenone may be sufficient to achieve the desired therapeutic response.

An increase in plasma levels of propafenone may occur when used concomitantly with paroxetine, so the dose of propafenone should be reduced.

The simultaneous use of propafenone hydrochloride and ritonavir at a dose of 800-1200 mg/day is contraindicated due to the potential increase in plasma concentrations.

Side effects of the drug Propafenone

Rarely observed. When taking propafenone in high doses, anorexia, a feeling of fullness in the stomach, nausea, vomiting, a bitter taste and a feeling of numbness in the mouth may occur; in isolated cases, decreased visual acuity, headache, anxiety, fear, sleep disturbance, confusion, and extrapyramidal symptoms were observed. Skin manifestations of allergic reactions are sometimes observed. In elderly patients, orthostatic disorders may occur, in rare cases - bradycardia, conduction disturbances of the sinus and AV nodes; The severity of heart failure may also increase. In rare cases, cholestasis is observed, which is independent of the dose and disappears after discontinuation of the drug. Taking propafenone in high doses can cause a decrease in potency. Leukopenia, granulocytopenia, and thrombocytopenia are very rarely observed. The composition of peripheral blood is normalized after discontinuation of propafenone.

Drug interactions Propafenone

When using local anesthetics simultaneously, as well as drugs that reduce heart rate and inhibit myocardial contractility (beta-adrenergic receptor blockers, tricyclic antidepressants), it is necessary to take into account the possibility of mutually enhancing the effect. Cases of increased plasma levels of propranolol, metoprolol and digoxin with simultaneous use of propafenone have been described. If signs of overdose appear, the content of drugs in the blood plasma should be monitored and, if necessary, their doses should be reduced. There are reports of an increase in the level of propafenone in the blood when it is used simultaneously with cimetidine, an increase in prothrombin time when combined with indirect anticoagulants.