Propafenone: Class 1c Antiarrhythmic Agent in Atrial Fibrillation and SVT

Propafenone is a sodium channel blocker of the Vaughan Williams class 1c and is used for pharmacological conversion and maintenance of sinus rhythm in paroxysmal atrial fibrillation and supraventricular tachycardias. Known brand names include Rytmonorm and propafenone generics. The substance was first approved in Germany in 1977.

A special feature is the so-called pill in the pocket concept: patients with infrequent paroxysmal atrial fibrillation can take propafenone as self-medication during an episode to restore sinus rhythm without hospitalization. This strategy is only established after initial successful and hospital-monitored trial administration.

Mechanism of Action

Propafenone blocks voltage-dependent sodium channels and thereby slows the rate of rise of the action potential in atrial, ventricular, and conduction fibers. The class 1c property means strong sodium channel blockade with only minimal effect on action potential duration. The consequence is significant slowing of conduction velocity in all cardiac tissues, which interrupts reentrant tachycardias and can restore sinus rhythm.

Additionally, propafenone has weak beta-blocking activity (approximately one tenth the potency of propranolol), which reduces heart rate and can enhance its effect in supraventricular tachycardias. An active metabolite (5-hydroxypropafenone) contributes significantly to the effect and is formed via CYP2D6.

Pharmacokinetically, propafenone shows pronounced interindividual variability due to CYP2D6 polymorphism. In extensive metabolizers (approximately 90 percent of the population), bioavailability is about 12 percent; in poor metabolizers (5 to 10 percent), up to 100 percent. Half-life 2 to 10 hours, which is why extended-release formulations are often preferred.

Indications

• Paroxysmal atrial fibrillation: pharmacological conversion and recurrence prophylaxis
• Pill in the pocket strategy: self-medication for infrequent paroxysmal atrial fibrillation
• Atypical atrial flutter
• Supraventricular tachycardias: AVNRT and AVRT in Wolff-Parkinson-White syndrome
• Symptomatic ventricular ectopic beats: in structurally normal heart

In structurally damaged heart (e.g., after myocardial infarction, heart failure with reduced LVEF), propafenone is contraindicated due to increased proarrhythmic effect (CAST trial 1989, which demonstrated increased mortality for class 1c antiarrhythmics).

Dosage and Administration

Oral maintenance therapy: 150 to 300 mg three times daily, standard usually 150 mg twice to three times daily. Extended-release form (Rytmonorm SR): 225 to 425 mg twice daily.

Pill in the pocket strategy: 450 mg (body weight less than 70 kg) or 600 mg (over 70 kg) as single oral dose during an episode, repeatable earliest after 4 hours if needed (total not more than 1,500 mg in 24 hours). Initial hospital trial administration with ECG monitoring is mandatory before use.

Intravenous conversion: 1.5 to 2 mg/kg over 10 minutes under ECG monitoring, in hospital. Renal insufficiency and hepatic insufficiency: reduce dose, use caution with severe impairment.

Adverse Effects

Frequent: taste disturbance with metallic taste, nausea, dizziness, headache, fatigue, visual disturbances, mild rash.

Serious: proarrhythmia with worsening of existing or triggering of new arrhythmias (typically atypical atrial flutter with 1:1 conduction and consecutive tachycardia, ventricular tachycardias); AV block, bradycardia, sinus arrest, heart failure deterioration; bronchospasm from beta-blocking component; lupus erythematosus-like syndrome.

Important: the proarrhythmic effect is the most important safety concern with propafenone and makes careful patient selection (structurally normal heart) and initial ECG monitoring mandatory.

Drug Interactions

• Other class 1 or class 3 antiarrhythmics (amiodarone, sotalol, flecainide): additive proarrhythmic effect, avoid combination
• Beta-blockers: additive beta-blockade, risk of bradycardia and AV block
• Digoxin: propafenone increases digoxin levels by approximately 70 percent, level monitoring required
• Warfarin: increased INR through inhibition of warfarin metabolism
• CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine): increased propafenone levels
• SSRI and antidepressants: increased propafenone levels and additive proarrhythmic effect
• Cimetidine: increased propafenone levels

Special Precautions

Pregnancy and lactation: data limited. Possible in critical indications and with careful benefit-risk assessment. Use possible during lactation, monitor infant.

Before starting therapy: ECG with assessment of QRS width (contraindication in bundle branch block), QTc interval, echocardiography for assessment of LVEF, electrolytes. Propafenone is contraindicated with reduced LVEF below 35 percent or structurally damaged heart.

Pill in the pocket prerequisite: initial use in hospital setting with ECG monitoring to test tolerability and efficacy, and to identify proarrhythmic reactions early.

Monitoring: ECG 1 to 2 weeks after start of therapy, then every 3 to 6 months depending on course. If QRS widens more than 25 percent compared to baseline ECG, reassess therapy.

You May Also Be Interested In

• Flecainide, another class 1c antiarrhythmic
• Amiodarone, class 3 antiarrhythmic in structurally damaged heart
• Sotalol, beta-blocker with class 3 effect
• Bisoprolol, beta-1 selective beta-blocker
• Digoxin, rate control in atrial fibrillation

Frequently Asked Questions

References

• ESC Guideline Atrial Fibrillation
• Gelbe Liste, Propafenone Active Ingredient Profile
• BfArM, Federal Institute for Drugs and Medical Devices
• EMA Product Information for Propafenone Preparations