What are the effects and dosing of propafenone (anti-arrhythmic medication) for treating irregular heartbeats?

Propafenone for Irregular Heartbeats

Propafenone is an effective Class IC antiarrhythmic agent for converting recent-onset atrial fibrillation and preventing recurrences in patients WITHOUT structural heart disease, ischemic heart disease, or left ventricular dysfunction. 1

Mechanism and Pharmacology

Propafenone works by reducing the fast inward sodium current in cardiac tissue, which slows conduction velocity and prolongs the effective refractory period. 2 It also possesses weak beta-blocking activity (approximately 1/40th the potency of propranolol) and mild local anesthetic effects. 2 The drug exhibits dose-dependent, nonlinear pharmacokinetics with wide inter-individual variation in plasma concentrations, requiring careful dose titration. 3

Dosing Regimens

Acute Conversion of Recent-Onset Atrial Fibrillation

For intravenous use: 2 mg/kg administered over 10-20 minutes achieves conversion rates of 41-91% within a few hours, compared to 10-29% with placebo. 1 Most conversions occur within the first hour after administration. 1

For oral loading ("pill-in-the-pocket"): 450-600 mg as a single dose achieves conversion rates of 72-78% within 8 hours. 1, 4 This approach should only be used after demonstrating safety in a monitored setting first. 5

Chronic Maintenance Therapy

For preventing recurrences: Start with 300 mg twice daily (BID). 1, 6 This dose is effective and well-tolerated, with a relative risk of treatment failure 6.8 times higher with placebo compared to propafenone. 6

Higher dose option: 300 mg three times daily (TID) may be more effective but causes more adverse effects. 1, 6 Use this dose only in patients who tolerate the lower dose but continue to have breakthrough arrhythmias. 6

Sustained-release formulation: 225-425 mg twice daily delays symptomatic recurrence and reduces ventricular rate during relapse. 1

Critical Contraindications

Propafenone is absolutely contraindicated in the following patients: 5, 7

• Structural heart disease (especially left ventricular dysfunction or heart failure)
• Ischemic heart disease or coronary artery disease (due to high proarrhythmic risk demonstrated in CAST-like scenarios)
• Significant sinus or AV conduction disease
• Cardiogenic shock or hypotension
• Brugada syndrome
• Severe obstructive lung disease

The contraindication in structural heart disease is absolute because propafenone exerts negative inotropic effects and increases mortality risk in these populations. 5, 7

Efficacy Comparisons

Propafenone demonstrates comparable or superior efficacy to other antiarrhythmics in specific contexts:

• Versus sotalol: Equally effective for maintaining sinus rhythm (30% vs 37% at 12 months). 1
• Versus quinidine: More effective with fewer side effects. 1
• Versus amiodarone: Less effective but with fewer side effects in the CTAF trial. 5
• Versus dofetilide: Equally effective for PSVT suppression. 1

Monitoring Requirements

ECG monitoring is mandatory during initiation and dose adjustments. 5, 7 Specifically monitor for:

• QRS duration: An increase >25% from baseline indicates potential proarrhythmic risk and requires dose reduction or discontinuation. 5, 7
• PR interval prolongation: Expected dose-related effect but monitor for excessive prolongation. 2
• Ventricular arrhythmias: Proarrhythmic effects occur in 1-5% of patients, including ventricular tachycardia and ventricular fibrillation. 7

Critical Adverse Effects and Management

Atrial flutter with 1:1 AV conduction is a potentially dangerous complication occurring in 3.5-5% of patients. 4 However, hemodynamically significant 1:1 conduction is rare (0.3% incidence). 4 Consider combining with AV nodal blocking agents (beta-blockers or calcium channel blockers) to prevent rapid ventricular response if flutter develops. 1

Negative inotropic effects can precipitate or worsen heart failure, which is why patients with any degree of ventricular dysfunction must be excluded. 2

Non-cardiovascular side effects (neurological, gastrointestinal) occur but are generally well-tolerated and resolve with continued therapy or dose reduction. 3

Drug Interactions

Propafenone increases serum digoxin levels, requiring digoxin dose adjustment when used concomitantly. 5 The drug is metabolized via CYP2D6, so poor metabolizers will have higher plasma concentrations and may require lower doses. 3

Clinical Positioning

Propafenone is first-line therapy for symptomatic paroxysmal atrial fibrillation in patients with structurally normal hearts. 5 It is particularly effective for:

• Recent-onset atrial fibrillation (<48 hours duration) 1
• Paroxysmal supraventricular tachycardia (PSVT) 1, 6
• Wolff-Parkinson-White syndrome with accessory pathway-mediated tachycardias 1

Propafenone has limited efficacy for: 1

• Persistent atrial fibrillation
• Atrial flutter (though it may convert some cases)

Common Pitfalls to Avoid

Do not use propafenone as first-line therapy in patients with any structural heart disease, even if mild—this includes hypertensive heart disease with LV hypertrophy or any degree of systolic dysfunction. 5, 7 The risk of proarrhythmic death outweighs potential benefits in these populations.

Do not initiate "pill-in-the-pocket" therapy without first observing the patient in a monitored setting to ensure they do not develop atrial flutter with rapid conduction or other serious adverse effects. 5

Do not ignore QRS widening—if QRS duration increases by more than 25% from baseline, reduce the dose or discontinue the drug immediately. 5, 7