Propanorm, 150 mg 50 pcs.

Propanorm is an antiarrhythmic.

Pharmacodynamics

The IC class antiarrhythmic drug, blocks fast sodium channels. It has weak beta-adrenoblocking activity and m-cholinoblocking action. Antiarrhythmic effect is based on local anesthetic and direct membrane stabilizing effect on myocardiocytes as well as on blockade of beta-adrenoreceptors and calcium channels.

Causes dose-dependent decrease in depolarization rate, inhibits phase 0 action potential and its amplitude in Purkinje fibers and ventricular contractile fibers, inhibits automatism. Delays conduction along Purkinje fibers. It prolongs conduction time through the sinoatrial (SA) node and atria. When propafenone is used, the PQ interval is prolonged and the QRS complex is widened (15 to 25), as well as the AH and HV intervals. The drug prolongs the effective refractory period in the atria, AV node, accessory bundles and, to a lesser extent, in the ventricles. No significant changes in the QT interval are observed. Electrophysiological effects are more pronounced in ischemic than in normal myocardium. It has a negative inotropic effect, which is usually manifested when left ventricular ejection fraction decreases below 40%.

The action begins 1 h after oral administration, reaches a maximum after 2-3 h and lasts 8-12 h.

Pharmacokinetics

The absorption of more than 95% of the drug. Propafenone exhibits dose-dependent bioavailability, which increases nonlinearly with increasing dose: it increases from 5% to 12% when the single dose is increased from 150 to 300 mg, and from 450 mg to 40-50%. C_max in plasma after oral administration is reached within 1-3.5 h and ranges from 500 to 1500 µg/L. The permeability through the HEB and the placental barrier is low. The volume of distribution is 3-4 l/kg. Binding with plasma proteins and internal organs (liver, lungs, etc.) is 85-97%.

Therapeutic range of propafenone concentration in blood plasma is 0.5-2.0 mg/l. Propafenone is almost completely metabolized. Eleven metabolites of the drug have been described – 5-hydoxypropafenone and N-depropylpropafenone are pharmacologically active, having antiarrhythmic activity comparable to propafenone. T_1/2 “fast metabolizers” is 2-10 h, “slow” – 10-32 h, biologicalT_1/2 is about 6.2 h. Excretion: by kidneys – 38% as metabolites (less than 1% unchanged), in the bile – 53% (as glucuronides and sulfates). In hepatic insufficiency the excretion decreases.

Indications

Prevention and treatment of supraventricular and ventricular extrasystoles, paroxysmal rhythm disturbances (supraventricular – atrial fibrillation and flutter, WPW syndrome), atrioventricular re-entry tachycardia;

prevention of sustained monomorphic ventricular tachycardia.

Pharmacological effect

Propanorm – antiarrhythmic.

Pharmacodynamics

Class IC antiarrhythmic drug, blocks fast sodium channels. It has weak beta-adrenergic blocking activity and m-anticholinergic action. The antiarrhythmic effect is based on local anesthetic and direct membrane-stabilizing effects on myocardiocytes, as well as on the blockade of beta-adrenergic receptors and calcium channels.

Causes a dose-dependent decrease in the rate of depolarization, inhibits phase 0 of the action potential and its amplitude in Purkinje fibers and contractile fibers of the ventricles, and inhibits automaticity. Slows down conduction along Purkinje fibers. Prolongs conduction time through the sinoatrial (SA) node and atria. When using propafenone, the PQ interval prolongs and the QRS complex expands (from 15 to 25), as well as the AH and HV intervals. The drug prolongs the effective refractory period in the atria, AV node, accessory bundles and, to a lesser extent, in the ventricles. There are no significant changes in the QT interval. 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 action begins 1 hour after oral administration, reaches a maximum after 2–3 hours and lasts 8–12 hours.

Pharmacokinetics

More than 95% of the drug is absorbed. Propafenone exhibits dose-dependent bioavailability, which increases nonlinearly with increasing dose: it increases from 5 to 12% when increasing a single dose from 150 to 300 mg, and at 450 mg – to 40–50%. Cmax in blood plasma after oral administration is achieved within 1–3.5 hours and ranges from 500 to 1500 mcg/l. Permeability through the BBB and placental barrier is low. Volume of distribution: 3–4 l/kg. Communication with proteins of blood plasma and internal organs (liver, lungs, etc.) – 85–97%.

The therapeutic range for propafenone plasma concentrations is 0.5–2.0 mg/L. Propafenone is almost completely metabolized. 11 metabolites of the drug have been described: 5-hydroxypropafenone and N-depropylpropafenone are pharmacologically active and have antiarrhythmic activity comparable to propafenone. T1/2 of “fast metabolizers” is 2-10 hours, “slow” – 10-32 hours, biological T1/2 is about 6.2 hours. Excreted by the kidneys – 38% in the form of metabolites (less than 1% unchanged), with bile – 53% (in the form of glucuronides and sulfates). In liver failure, excretion is reduced.

Special instructions

During the course of treatment, especially at the beginning of therapy, ECG monitoring is necessary.

It is recommended to begin treatment in a hospital setting, since the risk of arrhythmogenic effects associated with the use of propafenone is increased.

Propanorm should be used under the control of blood electrolyte balance (especially potassium concentration) and ECG; 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.

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

It is necessary to conduct clinical and laboratory monitoring of patients undergoing long-term treatment with anticoagulants and hypoglycemic drugs while using Propanorm.

If during treatment sinoatrial blockade or AV block of the third degree, or frequently recurring extrasystole are noted, the treatment must be interrupted.

Considering the possibility of proarrhythmogenic effects, the drug is recommended to be used only as directed and under the supervision of a physician.

– Use for liver dysfunction: In patients with liver failure, the bioavailability of propafenone increases by 70%; in such patients it is recommended to reduce the dose and regularly monitor laboratory parameters. In case of liver dysfunction (cumulation is possible), Propanorm is used in doses of 20-30% of the usual dose.

– Use for impaired renal function: In case of impaired renal function (creatinine clearance < 10 ml/min), the initial dose is 50% of the original.

Impact on the ability to drive vehicles or operate machinery: 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.

Active ingredient

Propaphenone

Composition

Active ingredient:

propafenone hydrochloride 150 mg;

Excipients:

Microcrystalline granulated cellulose,

corn starch,

copovidon,

sodium croscarmellose,

magnesium stearate,

sodium lauryl sulfate,

hypromellose 5,

macrogol 6000,

titanium dioxide,

emulsion of dimethicone with silicon dioxide.

Pregnancy

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.

Contraindications

hypersensitivity to the components of the drug;
digoxin intoxication;
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 severe arterial hypotension;
SA blockade, intraatrial conduction disorder; bundle branch block; intraventricular bifascicular block and AV block of II–III degree (without pacemaker);
sick sinus syndrome; “tachycardia-bradycardia” syndrome;
myocardial infarction;
lactation period;
age under 18 years (efficacy and safety have not been established).

With caution:

chronic obstructive pulmonary disease (COPD);
myasthenia gravis (including myasthenia gravis);
heart failure (ejection fraction less than 30%), cardiomyopathy, arterial hypotension, presence of a permanent or temporary pacemaker;
hepatic cholestasis, liver and/or renal failure;
combination with other antiarrhythmic drugs that have similar effects on cardiac electrophysiology;
electrolyte disturbances (must be corrected before prescribing propafenone);
age over 70 years.

Side Effects

From the cardiovascular system: bradycardia, AV dissociation, ventricular tachyarrhythmias, angina pectoris, worsening of heart failure (in patients with reduced left ventricular function), sinoatrial block, AV block, intraventricular conduction disorders, supraventricular tachyarrhythmias, when taken in high doses – orthostatic hypotension.

From the digestive system: change in taste, dry mouth, bitterness in the mouth, nausea, decreased appetite, feeling of heaviness in the epigastrium, constipation or diarrhea; rarely – liver dysfunction, cholestatic jaundice, cholestasis.

From the side of the central nervous system: headache, dizziness; rarely – blurred vision, diplopia, convulsions.

From the hematopoietic system: leukopenia, agranulocytosis, increased bleeding time, thrombocytopenia, the appearance of antinuclear antibodies.

From the reproductive system: oligospermia, decreased potency.

Allergic reactions: skin rash, itching, exanthema, redness of the skin, urticaria, lupus-like syndrome.

Other: weakness, bronchospasm, hemorrhagic skin rashes.

Interaction

You cannot combine Propanorm with lidocaine, because the cardiodepressive effect is enhanced.

With simultaneous use, propafenone increases the concentration of propranolol, metoprolol, digoxin (increases the risk of developing glycoside intoxication), indirect anticoagulants, and cyclosporine in the blood plasma.

When used simultaneously, propafenone enhances the effect of warfarin (by blocking metabolism).

When used simultaneously with beta-blockers, tricyclic antidepressants, the antiarrhythmic effect may be enhanced.

When used simultaneously with local anesthetics, the risk of central nervous system damage increases.

Cimetidine and quinidine, by slowing metabolism, increase the concentration of propafenone in plasma by 20%, rifampicin reduces it.

When used simultaneously with propafenone, amiodarone increases the risk of developing pirouette-type tachycardia.

Drugs that suppress the sinoatrial node and AV node and have a negative inotropic effect, when used simultaneously with propafenone, increase the risk of side effects.

Drugs that inhibit bone marrow hematopoiesis, when used simultaneously with propafenone, increase the risk of myelosuppression.

Overdose

When taking a dose twice the daily dose at once, symptoms of intoxication may appear after 1 hour, or at most after a few hours.

Symptoms: persistent decrease in blood pressure, nausea, dry mouth, vomiting, mydriasis, drowsiness, extrapyramidal disorders, confusion, bradycardia, prolongation of the QT interval, intra-atrial and intraventricular conduction disorders, ventricular tachyarrhythmias, paroxysms of polymorphic ventricular tachycardia, sinoatrial block, AV block, asystole, coma, convulsions, delirium, pulmonary edema.

Treatment: gastric lavage, defibrillation, administration of dobutamine, diazepam; if necessary – mechanical ventilation and indirect cardiac massage. Hemodialysis is ineffective.

Storage conditions

In a dry place, protected from light, at a temperature of 15–25 °C

Shelf life

3 years

Manufacturer

PRO.MED.CS Prague, Czech Republic