How should flecainide be started, titrated, and monitored in an adult with Wolff‑Parkinson‑White syndrome who has no structural heart disease, coronary artery disease, heart failure, left‑ventricular dysfunction, Brugada pattern, or severe hepatic or renal impairment?

Flecainide Administration in Wolff-Parkinson-White Syndrome

In an adult with WPW syndrome and no structural heart disease, start flecainide at 50 mg every 12 hours, increase by 50 mg twice daily every 4 days as needed up to a maximum of 150 mg every 12 hours (300 mg/day), with baseline ECG and monitoring for QRS widening and proarrhythmic effects. 1

Pre-Treatment Assessment and Contraindication Screening

Before initiating flecainide, you must confirm the absence of:

• Structural heart disease, coronary artery disease, or reduced ejection fraction – these are absolute contraindications and were associated with increased mortality in the CAST trial 2, 1, 3
• Sinus or AV node dysfunction – flecainide can worsen conduction abnormalities 1, 2
• Brugada pattern on ECG – flecainide can unmask this syndrome 4
• Baseline QTc >500 ms – indicates increased proarrhythmic risk 5
• Severe renal or hepatic impairment – requires dose adjustment or avoidance 3

Obtain a baseline ECG specifically measuring QTc, QRS duration, and PR interval before starting therapy 5, 6

Starting Dose and Titration Protocol

Initial dose: 50 mg orally every 12 hours (100 mg/day total) 6, 1

Titration schedule:

• Increase by 50 mg twice daily (100 mg/day increments) every 4 days until efficacy is achieved 6, 1
• The 4-day interval is critical because flecainide has a half-life of 12-27 hours, and steady-state plasma levels require 3-5 days at a given dose 1

Maximum dose: 150 mg every 12 hours (300 mg/day total) for paroxysmal supraventricular arrhythmias including WPW 6, 1

Monitoring Requirements During Titration

ECG monitoring during dose increases:

• Monitor PR and QRS intervals with each dose escalation 6
• Discontinue if QRS widens by >25% from baseline – this indicates excessive sodium channel blockade 1
• Watch for QTc >500 ms, though note that 60-90% of QT widening with flecainide is due to QRS prolongation, not true repolarization delay 5

Plasma level monitoring (optional but recommended):

• Keep trough levels below 0.7-1.0 mcg/mL 6
• This is particularly important in patients with renal dysfunction or those on CYP2D6 inhibitors 6, 3

Critical Safety Considerations Specific to WPW

Concomitant AV nodal blocking therapy is mandatory:

• Always add a beta-blocker or non-dihydropyridine calcium channel blocker (diltiazem or verapamil) when using flecainide in WPW 7
• This prevents the potentially lethal complication of atrial flutter with 1:1 AV conduction, which can occur when flecainide slows atrial rate enough to allow 1:1 conduction through the AV node 6, 7
• Concomitant beta-blocker use also improves long-term efficacy 7

Avoid these drugs in WPW with pre-excited AF:

• IV amiodarone, adenosine, digoxin, or non-dihydropyridine calcium channel blockers are potentially harmful as they can accelerate ventricular rate through the accessory pathway 2
• However, oral flecainide with AV nodal blockade is appropriate for chronic management 7

Acute Cardioversion Dosing (Alternative Approach)

For acute conversion of pre-excited AF in WPW:

Intravenous route: 1.5-3.0 mg/kg over 10-20 minutes terminates tachycardia in >80% of cases 6, 7

Oral single loading dose: 200-300 mg (or 4 mg/kg, maximum 300 mg) for pharmacological cardioversion 6, 8

The "pill-in-the-pocket" approach is reasonable once safety has been demonstrated in a monitored setting 6

Drug Interactions Requiring Dose Adjustment

CYP2D6 inhibitors (quinidine, fluoxetine, tricyclic antidepressants) can dramatically increase flecainide plasma levels:

• CYP2D6 is genetically absent in 7-10% of the population 6
• Reduce flecainide dose by 30-50% when adding these medications 4, 6

Amiodarone: Reduce flecainide dose by 30-50% due to pharmacokinetic interaction 4

Digoxin: Flecainide increases digoxin levels by 30-50%; monitor digoxin concentrations 4, 6

Expected Efficacy and Long-Term Management

Acute efficacy in WPW:

• Flecainide blocks anterograde accessory pathway conduction in 40% and retrograde conduction in 50% of cases 7
• Markedly prolongs refractoriness in remaining cases 7

Chronic efficacy:

• Prevents clinical recurrences in >60% of cases with oral therapy 7
• Long-term efficacy is predicted by abolition of accessory pathway conduction or prevention of tachycardia induction at electrophysiologic testing 7

Monitoring after stabilization:

• Once adequate arrhythmia control is achieved, consider reducing dose to minimize side effects while maintaining efficacy 1
• Some patients may require dosing every 8 hours instead of every 12 hours for adequate control 1

Common Adverse Effects and Management

Most frequent non-cardiac effects:

• Dizziness and visual disturbances (blurred vision, difficulty focusing) are most common but usually mild, transient, and tolerable 3

Cardiac adverse effects to monitor:

• Proarrhythmia occurs in 7-8% overall, but almost exclusively in patients with structural heart disease (which you've excluded) 9, 3
• Conduction abnormalities (PR/QRS prolongation) 3
• Negative inotropic effects (minimal concern in structurally normal hearts) 9

When to Consider Catheter Ablation Instead

Catheter ablation of the accessory pathway is recommended (Class I indication) in symptomatic WPW patients, especially if:

• The accessory pathway has a short refractory period allowing rapid antegrade conduction 2
• The patient has pre-excited AF 2
• Medical therapy fails or is not tolerated 2

Ablation offers definitive cure and should be discussed as a first-line option in symptomatic WPW patients 2