What is Flecainide?

What is Flecainide

Flecainide is a Class IC antiarrhythmic drug that blocks cardiac sodium channels (Nav1.5), slowing electrical conduction throughout the heart, particularly in the His-Purkinje system and ventricles. 1

Mechanism of Action and Electrophysiology

Flecainide belongs to the membrane-stabilizing class of antiarrhythmics with local anesthetic properties. 1 The drug produces dose-related decreases in intracardiac conduction in all parts of the heart, with the most pronounced effects on:

• His-Purkinje system (H-V conduction) - greatest impact 1
• Ventricular conduction velocity - significant slowing 1
• AV nodal and intra-atrial conduction - less pronounced effects 1
• Ventricular refractory periods - significant prolongation 1

On ECG, flecainide characteristically prolongs the PR interval and widens the QRS complex. 1, 2

Clinical Indications

Primary Uses (Guideline-Supported)

Flecainide is recommended as second-line therapy for supraventricular arrhythmias in patients without structural or ischemic heart disease. 3, 4

The American College of Cardiology/American Heart Association provides a Class IIa recommendation for flecainide in AVNRT/AVRT management when: 3, 4

• No structural heart disease is confirmed
• No ischemic heart disease is present
• First-line agents (beta-blockers, diltiazem, or verapamil) are ineffective or contraindicated
• Patient is not a candidate for or refuses catheter ablation

Flecainide demonstrates 93% probability of effective treatment (defined as <2 attacks of arrhythmia) at 12 months for AVNRT. 3

Specific Arrhythmia Applications

• Paroxysmal atrial fibrillation - cardioversion of recent-onset AF and maintenance of sinus rhythm 5, 6
• AVNRT (atrioventricular nodal re-entrant tachycardia) - 30% achieve complete symptomatic suppression versus 13% with verapamil 3, 4
• AVRT (atrioventricular re-entrant tachycardia) - renders sustained tachycardia non-inducible in 85% of patients 4
• Ventricular arrhythmias - only in patients without structural heart disease 6

Efficacy Data

When combined with beta-blockers, flecainide achieves >90% efficacy for abolition of symptomatic tachycardia. 4 This combination also reduces the risk of 1:1 AV conduction if atrial flutter develops. 3, 4

Flecainide shows superiority over placebo with only 24% recurrence rate versus 85% on placebo in controlled trials for paroxysmal supraventricular tachycardia. 4

Pharmacokinetics

• Absorption: Nearly complete oral absorption with peak plasma levels at 3 hours (range 1-6 hours) 1
• Half-life: Approximately 20 hours (range 12-27 hours), allowing twice-daily dosing 1, 7
• Steady-state: Achieved in 3-5 days with multiple dosing 1
• Therapeutic plasma levels: 0.2 to 1 mcg/mL for maximal therapeutic effect 1
• Metabolism: 30% excreted unchanged in urine; two major metabolites (one active but less potent, one inactive) 1
• No first-pass effect: Food and antacids do not affect absorption (though milk may inhibit absorption in infants) 1

Critical Contraindications

Flecainide is absolutely contraindicated in patients with structural heart disease or ischemic heart disease due to proarrhythmic risk demonstrated in the CAST trial. 3, 4, 5

The Cardiac Arrhythmia Suppression Trial (CAST) showed that flecainide and encainide increased mortality in patients with:

• Frequent ventricular ectopics
• Reduced left ventricular function
• Prior myocardial infarction 5, 8

Additional contraindications include: 9, 4

• Coronary artery disease
• Reduced left ventricular ejection fraction
• Significant structural heart disease

Proarrhythmic Risks and Monitoring

Plasma levels above 0.7 to 1 mcg/mL are associated with higher rates of cardiac adverse events including conduction defects and bradycardia. 1

Specific Proarrhythmic Concerns

• QRS prolongation >25% from baseline indicates potential proarrhythmia risk and requires dose reduction or discontinuation 9
• Conversion of atrial fibrillation to atrial flutter with rapid ventricular conduction is a dangerous complication requiring specialist expertise 9
• Ventricular arrhythmias can develop even with normal baseline ECG and no QTc prolongation 2

Required Monitoring

The European Heart Journal recommends: 9

• Comprehensive cardiac assessment before initiation to rule out structural heart disease
• Regular ECG monitoring, particularly when initiating treatment or adjusting dosage
• QRS duration monitoring with dose reduction if QRS widens by >25% from baseline
• Initial in-hospital evaluation for "pill-in-the-pocket" approach

Adverse Effects

Dizziness is the most frequent non-cardiac side effect, followed by blurred vision and difficulty focusing. 8 These are typically mild, transient, and tolerable. 8

Cardiac adverse effects include: 8

• Proarrhythmia (7-8% of patients, higher in those with serious ventricular tachycardia and reduced myocardial function) 7
• Conduction abnormalities 8
• Negative inotropic effects (can become clinically significant in patients with impaired ventricular function) 1, 7

Drug Interactions and Combination Therapy

Combination with beta-blockers is recommended to enhance efficacy and reduce risk of 1:1 AV conduction if atrial flutter develops. 3, 4 This combination increases success rates to >90% for AVRT. 4

• Isoproterenol partially reverses the electrophysiological effects of flecainide 4
• Adenosine should be used with caution as it may precipitate atrial fibrillation with rapid ventricular rate in pre-excited tachycardias 4
• Concomitant AV nodal blocking agents are often required, adding complexity to the medication regimen 9

Special Populations

• Renal dysfunction: Caution required with dose adjustments 8
• Children: May be used for some supraventricular tachycardias 6
• Pregnancy: Can be used for sustained fetal tachycardia 6
• Adult congenital heart disease: Contraindicated in those with significant ventricular dysfunction 9

Clinical Implications for Management

The European Society of Cardiology and American College of Cardiology emphasize that flecainide requires careful patient selection and specialized cardiac evaluation, best accomplished by cardiologists specializing in cardiac arrhythmias. 9, 4

The drug has been available in clinical practice for over 40 years with a well-established safety profile when used in appropriately selected patients without structural heart disease. 8, 6