Propafenone (Tablets, Solution) Instructions for Use

ATC Code

C01BC03 (Propafenone)

Active Substance

Propafenone (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antiarrhythmic drug. Class I C

Pharmacotherapeutic Group

Means for the treatment of heart diseases; antiarrhythmic agents, class IC

Pharmacological Action

Propafenone is a class IC antiarrhythmic agent, a sodium channel blocker. It reduces the maximum rate of depolarization of phase 0 of the action potential and its amplitude, primarily in Purkinje fibers and ventricular contractile fibers, and decreases automaticity.

It is highly effective in ventricular arrhythmias; its efficacy in supraventricular rhythm disorders is somewhat lower. Propafenone has a weakly expressed beta-adrenergic blocking effect.

Pharmacokinetics

The pharmacokinetics of propafenone are characterized by significant individual variations.

After oral administration, absorption is rapid and almost complete – more than 90%. C_max in blood plasma is reached in 1-3.5 hours. Protein binding is 97%.

It undergoes intensive metabolism during the first pass through the liver with the formation of 2 active metabolites – 5-hydroxypropafenone and N-depropylpropafenone, which have antiarrhythmic activity comparable to that of propafenone but are present in concentrations amounting to 20% of propafenone concentrations.

T_1/2 in patients with intensive metabolism (more than 90% of cases) is 2-10 hours, and in those with slow metabolism (less than 10% of cases) it is 10-32 hours.

It is excreted by the kidneys – 38% as metabolites, 1% unchanged; through the intestines – 53% as metabolites.

Indications

Treatment and prevention of supraventricular and ventricular extrasystoles, paroxysmal rhythm disorders (supraventricular tachycardia, including in WPW syndrome; ventricular tachycardia).

ICD codes

Dosage Regimen

For oral administration, initiate therapy with a total daily dose of 450 mg to 600 mg.

Divide the total daily dose into three equal administrations taken at approximately 8-hour intervals.

If adequate therapeutic effect is not achieved after 3-4 days, increase the dose gradually.

The maximum recommended daily dose is 900 mg.

For intravenous infusion, administer an initial dose of 500 mcg per kg of body weight.

If necessary, the intravenous dose may be increased to a range of 1 mg/kg to 2 mg/kg.

Administer the intravenous infusion slowly under continuous ECG and blood pressure monitoring.

In patients with hepatic impairment or severe renal impairment, use a reduced dose.

For elderly patients and patients with a body weight below 70 kg, initiate therapy at the lower end of the dosage range.

Discontinue previous antiarrhythmic therapy for a period equal to 2-5 half-lives before initiating propafenone.

If QRS complex or QT interval widens by more than 20%, reduce the dose or temporarily discontinue treatment.

Adverse Reactions

From the cardiovascular system: bradycardia, slowing of sinoatrial, AV, and intraventricular conduction, decreased myocardial contractility (in predisposed patients), arrhythmogenic action; when taken in high doses – orthostatic hypotension.

From the digestive system: when taken in high doses, nausea, anorexia, feeling of heaviness in the epigastrium, constipation are possible; rarely – impaired liver function.

From the central nervous system: when taken in high doses – headache, dizziness; rarely – visual impairment.

From the hematopoietic system: leukopenia, agranulocytosis, thrombocytopenia.

From the reproductive system: oligospermia.

Allergic reactions: rarely – skin rash.

Contraindications

Severe forms of chronic heart failure, pronounced arterial hypotension, cardiogenic shock, severe bradycardia, sick sinus syndrome, AV block of II and III degree, electrolyte imbalance, myasthenia gravis, severe obstructive pulmonary diseases, hepatic cholestasis, childhood, hypersensitivity to propafenone.

Use in Pregnancy and Lactation

Use during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.

If it is necessary to use during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Use with caution in cases of impaired liver function.

Use in Renal Impairment

Use with caution in cases of severe renal impairment.

Pediatric Use

Contraindicated in childhood.

Geriatric Use

In elderly patients, Propafenone should be used in lower doses.

Special Precautions

Use with caution in cases of impaired liver function, severe renal impairment, and also in combination with other antiarrhythmic agents with similar electrophysiological parameters.

Treatment should be initiated in a hospital setting due to the increased risk of arrhythmogenic action associated with the use of propafenone. It is recommended that prior antiarrhythmic therapy be discontinued before starting treatment with propafenone for a period equal to 2-5 T_1/2.

Propafenone is characterized by pronounced individual variations in the plasma concentrations of the active substance, so careful dose selection for each patient is recommended.

IV administration should be carried out under constant monitoring of blood pressure, heart rate, and ECG. If during the course of treatment or against the background of IV administration, a widening of the QRS complex or QT interval by more than 20% compared to the initial values is noted, the dose of Propafenone should be reduced or temporarily discontinued.

In elderly patients and patients with a body weight of less than 70 kg, Propafenone should be used in lower doses.

Effect on the ability to drive vehicles and operate machinery

Use with caution in patients engaged in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with anticholinergic agents, an enhancement of the anticholinergic effect is possible.

With simultaneous use with anticholinesterase agents (including pyridostigmine), the effectiveness of pyridostigmine in myasthenia gravis is reduced.

With simultaneous use with beta-blockers, tricyclic antidepressants, local anesthetics, an enhancement of the antiarrhythmic effect of propafenone in ventricular arrhythmias is possible.

Propafenone may potentiate the effect of indirect anticoagulants.

With simultaneous use with phenobarbital, the excretion of propafenone from the body increases and its concentration in blood plasma decreases. It is believed that other barbiturates interact with propafenone in the same way.

With simultaneous use with ketoconazole, a case of seizure development has been described.

With simultaneous use, an increase in plasma concentrations of propranolol, metoprolol, cyclosporine, digoxin is possible.

With simultaneous use with rifampicin, the concentration of propafenone in blood plasma decreases and its therapeutic efficacy is significantly reduced. This is due to the fact that rifampicin induces the CYP3A4/1A2 isoenzymes and phase II glucuronidation of propafenone. Rifampicin does not affect the metabolism of propafenone due to the activity of the CYP2D6 isoenzyme.

With simultaneous use, cases of increased plasma concentration of theophylline and the development of toxic reactions have been 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 plasma concentration. At the same time, the efficacy of propafenone does not change, since the production of its active metabolite (5-hydroxypropafenone) simultaneously decreases by 2 times.

Quinidine enhances the beta-blocking effects of propafenone in individuals with a high level of liver metabolism, since only the original active substance, and not the metabolites, has beta-blocking activity.

With simultaneous use with cimetidine, a slight increase in the plasma concentration of propafenone and widening of the QRS complex on the ECG are possible.

With simultaneous use, erythromycin may inhibit the metabolism of propafenone.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.