Rytmonorm^® (Tablets) Instructions for Use

Marketing Authorization Holder

Abbott Laboratories, GmbH (Germany)

Manufactured By

Famar Lyon (France)

ATC Code

C01BC03 (Propafenone)

Active Substance

Propafenone (Rec.INN registered by WHO)

Dosage Form

Rytmonorm®

Film-coated tablets, 150 mg: 20, 50, or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex, with an engraving “150” on one side.

Excipients: microcrystalline cellulose – 25.4 mg, croscarmellose sodium – 10 mg, corn starch – 20 mg, hypromellose 2910 – 8 mg, magnesium stearate – 0.5 mg, water – 6.1 mg.

Film coating composition: macrogol 400 – 0.52 mg, macrogol 6000 – 4.176 mg, hypromellose 2910 – 6.264 mg, titanium dioxide – 1.04 mg.

10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.

Clinical-Pharmacological Group

Antiarrhythmic drug. Class I C

Pharmacotherapeutic Group

Antiarrhythmic agent

Pharmacological Action

An antiarrhythmic agent of class IC, 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 effectiveness 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 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 constituting 20% of propafenone concentrations.

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

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

Initiate treatment with an initial oral dose of 150 mg three times daily (450 mg/day).

Increase the dose after 3-4 days to 300 mg twice daily (600 mg/day) if the clinical response is inadequate.

Do not exceed a maximum daily dose of 900 mg (300 mg three times daily).

Administer tablets whole with a sufficient amount of fluid after a meal.

For intravenous infusion, administer an initial dose of 500 mcg/kg over 10-20 minutes.

If necessary, repeat the intravenous dose at a rate of 1-2 mg/kg under continuous monitoring.

Adjust the dosage regimen individually based on therapeutic response and ECG parameters.

Reduce the dose in elderly patients, patients with hepatic impairment, or those weighing less than 70 kg.

Discontinue or reduce the dose if the QRS complex widens by more than 20%.

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 CNS 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 liver dysfunction.

Use in Renal Impairment

Use with caution in severe renal impairment.

Pediatric Use

Contraindicated in children.

Geriatric Use

In elderly patients, Propafenone is used in lower doses.

Special Precautions

Use with caution in liver dysfunction, severe renal impairment, and also in combination with other antiarrhythmic agents with similar electrophysiological parameters.

Treatment should be started in a hospital setting, since there is an 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 differences in the values of the active substance concentration in plasma, therefore careful dose selection for each patient is recommended.

Intravenous 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 intravenous administration, a widening of the QRS complex or QT interval by more than 20% is noted compared to the initial values, the dose of Propafenone should be reduced or temporarily discontinued.

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

Influence on the ability to drive vehicles and mechanisms

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 increase in anticholinergic action is possible.

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

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

With simultaneous use, 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 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 plasma decreases and its therapeutic effectiveness significantly decreases.

This is due to the fact that rifampicin induces isoenzymes CYP3A4/1A2 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 effectiveness of propafenone does not change, because the production of its active metabolite (5-hydroxypropafenone) simultaneously decreases by 2 times.

Quinidine increases the beta-blocking effects of propafenone in individuals with a high level of liver metabolism, because only the original active substance, and not 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 15°C (59°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.