What is propafenone?

What is Propafenone?

Propafenone is a Class IC antiarrhythmic drug with weak beta-blocking activity, indicated for preventing recurrent atrial fibrillation/flutter and supraventricular tachycardia in patients without structural heart disease, and for treating life-threatening ventricular arrhythmias. 1

Pharmacological Classification and Mechanism

Propafenone functions primarily as a sodium channel blocker (Class IC antiarrhythmic) with additional weak beta-adrenoceptor antagonist properties and mild calcium channel blocking effects. 2, 3 The drug demonstrates clinically significant beta-blockade at the 600 mg dose recommended for cardioversion, reducing heart rate by 6% and systolic blood pressure by 6% during exercise. 4

FDA-Approved Indications

The FDA has approved propafenone for three specific indications: 1

• Paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms in patients without structural heart disease
• Paroxysmal supraventricular tachycardia (PSVT) associated with disabling symptoms in patients without structural heart disease
• Life-threatening ventricular arrhythmias such as sustained ventricular tachycardia (hospital initiation required)

Clinical Efficacy Profile

Supraventricular Arrhythmias

Propafenone demonstrates robust efficacy for converting recent-onset atrial fibrillation and preventing recurrences. 5 The UK PSVT study established that 300 mg twice daily is effective, with 300 mg three times daily showing even greater efficacy but more frequent side effects. 5 In placebo-controlled trials, propafenone reduced days in atrial fibrillation from 51% to 27%. 5

For acute cardioversion, oral loading doses of 450-600 mg achieve conversion rates of 72-78% within 8 hours, compared to 10-29% with placebo. 6 Intravenous administration of 2 mg/kg over 10-20 minutes achieves conversion rates of 41-91% within a few hours. 6

Ventricular Arrhythmias

In non-comparative studies, propafenone 450-900 mg/day suppressed premature ventricular complexes and couplets in 75-96% of patients and abolished ventricular tachycardia in 75% of patients. 2 Placebo-controlled studies confirmed that propafenone 300-900 mg daily suppressed premature ventricular complexes (>80%) in 77% of patients. 2

Absolute Contraindications

Propafenone must never be used in the following patient populations: 5, 6, 1

• Patients with ischemic heart disease or coronary artery disease (increased risk of ventricular arrhythmias and sudden death)
• Patients with left ventricular dysfunction or heart failure (negative inotropic effects worsen cardiac function)
• Patients with significant structural heart disease
• Patients with significant sinus or AV conduction disease without a pacemaker
• Patients with Brugada syndrome
• Patients with severe obstructive lung disease

Critical Safety Requirements

Mandatory AV Nodal Blockade

Beta-blockers or non-dihydropyridine calcium channel blockers (diltiazem/verapamil) must be administered at least 30 minutes before propafenone to prevent 1:1 AV conduction during atrial flutter. 5, 6, 7, 8 This is non-negotiable because propafenone can convert atrial fibrillation to atrial flutter with paradoxically rapid ventricular rates. 8

The intrinsic beta-blocking activity of propafenone itself is insufficient to control AV nodal conduction during atrial fibrillation. 8

ECG Monitoring Requirements

QRS duration must be monitored and should not exceed a 25% increase from baseline—greater widening signals proarrhythmic risk requiring immediate dose reduction or cessation. 6, 7, 8 Regular ECG monitoring is mandatory during initiation and dose adjustments. 6

Proarrhythmic Risks

Propafenone carries a 1-5% risk of ventricular arrhythmias depending on dose, with higher risk in patients with structural heart disease. 7, 8 The first dose must be supervised in a hospital setting to assess for bradycardia, conduction abnormalities, or proarrhythmia before any "pill-in-the-pocket" home use. 6, 8

Dosing Regimens

For Prevention of Recurrences

Start at 150 mg every 8 hours (450 mg/day) and titrate upward every 3-4 days to a maximum of 300 mg every 8 hours (900 mg/day) based on response. 7 The sustained-release formulation can be dosed at 225-425 mg twice daily. 5

For Acute Cardioversion

• Oral loading: 450-600 mg as a single dose 6
• Intravenous: 2 mg/kg over 10-20 minutes 6

Comparative Effectiveness

Propafenone demonstrates comparable efficacy to sotalol (30% vs 37% maintaining sinus rhythm at 12 months) but is less effective than amiodarone (39% vs 69% at 16 months), though amiodarone has higher discontinuation rates due to side effects (18% vs 11%). 7 Propafenone is more effective than quinidine with fewer side effects. 5

Drug Interactions

Propafenone increases serum digoxin levels, requiring monitoring if both drugs are used concurrently. 6, 8 The combination of propafenone with digoxin and beta-blockers produces synergistic effects on the AV node. 8

Pharmacokinetic Considerations

Propafenone exhibits dose-dependent, nonlinear pharmacokinetics with wide interindividual variation in plasma concentrations (64-3271 micrograms/L after comparable doses). 2, 3 Metabolism is genetically determined, with poor debrisoquine metabolizers unable to oxidize the drug effectively. 2, 3 The drug has an active metabolite (5-hydroxypropafenone) that contributes to clinical effects. 2

Common Pitfalls to Avoid

• Never initiate propafenone without concurrent AV nodal blockade in patients at risk for atrial flutter 7, 8
• Never assume propafenone's intrinsic beta-blocking activity is sufficient for rate control—it is not 8
• Never use propafenone for rate control during atrial fibrillation—it is not indicated for this purpose 1
• Never prescribe outpatient "pill-in-the-pocket" without prior supervised hospital trial 6, 8