In a patient with atrial fibrillation, a structurally normal heart, no coronary artery disease, normal QT interval, and normal electrolytes, how should flecainide be dosed, monitored, and what are its contraindications?

Flecainide in Atrial Fibrillation

Dosing Recommendations

For patients with paroxysmal atrial fibrillation and a structurally normal heart, flecainide should be initiated at 50 mg orally every 12 hours, with dose increases of 50 mg twice daily every 4 days as needed, up to a maximum of 300 mg/day. 1

• The starting dose of 50 mg every 12 hours applies specifically to patients with paroxysmal supraventricular tachycardia (PSVT) and paroxysmal atrial fibrillation (PAF) 1
• Dose escalation should occur no more frequently than every 4 days because steady-state plasma levels require 3-5 days to achieve in patients with normal renal and hepatic function 1
• For acute cardioversion of recent-onset AF, a single oral loading dose of 200-300 mg can be administered once safety has been established in a monitored setting 2
• The "pill-in-the-pocket" approach using 200-300 mg orally is reasonable for terminating AF outside the hospital, but only after the safety of this regimen has been verified in a monitored setting 2

Mandatory Pre-Treatment Requirements

A beta-blocker or non-dihydropyridine calcium channel antagonist must be administered at least 30 minutes before flecainide to prevent atrial flutter with 1:1 atrioventricular conduction, which can cause life-threatening rapid ventricular rates. 2, 3

• This requirement applies to all patients except those with documented AV node conduction impairment 3
• Beta-blockers are preferred over calcium channel blockers because verapamil and diltiazem are moderate CYP3A4 inhibitors that can increase flecainide levels 3
• The only exception to mandatory AV nodal blockade is in patients with intrinsic AV nodal dysfunction who cannot conduct rapidly even if atrial flutter develops 3

Absolute Contraindications

Flecainide is absolutely contraindicated in patients with structural heart disease, including reduced left ventricular ejection fraction, history of myocardial infarction, coronary artery disease with ischemia, or significant left ventricular dysfunction. 2, 3

• The CAST trial demonstrated increased mortality with flecainide in patients with prior myocardial infarction and left ventricular dysfunction 4, 5
• Flecainide should be avoided in patients with sinus or AV node dysfunction, bundle branch block, or baseline QT prolongation 6
• Patients with Brugada syndrome should never receive flecainide as it can unmask this condition and cause sudden death 6
• Severe renal impairment (creatinine clearance <35 mL/min) requires dose adjustment or represents a relative contraindication 1

Monitoring Requirements

Before initiating flecainide, obtain a 12-lead ECG to assess baseline QRS duration and QT interval, verify normal serum electrolytes (potassium and magnesium), and check renal and hepatic function. 3, 7

• Baseline QRS duration should not increase by more than 25% from baseline during therapy 3
• Continuous ECG monitoring is required during the first dose administration to assess for proarrhythmic effects, bradycardia, and conduction abnormalities 6, 7
• After each dose change, monitor PR interval, QRS duration, and QT interval 7
• Plasma trough flecainide levels (obtained <1 hour pre-dose) should be checked at steady state, with therapeutic levels typically 200-500 ng/mL 1
• Approximately 7-10% of the population lacks CYP2D6 enzyme genetically, leading to higher drug levels and requiring closer monitoring 3

Critical Drug Interactions

Macrolide antibiotics (clarithromycin, erythromycin) and azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole) are absolutely contraindicated with flecainide due to CYP3A4 inhibition that dramatically increases flecainide levels and cardiac toxicity risk. 3

• Safe antibiotic options include beta-lactams (penicillins, cephalosporins, carbapenems), tetracyclines, sulfonamides, metronidazole, and linezolid 3
• Verapamil and diltiazem increase flecainide levels through CYP3A4 inhibition, making beta-blockers the preferred AV nodal blocking agents 3

Initiation Setting

Outpatient initiation of flecainide is reasonable in patients with paroxysmal AF who are in sinus rhythm at the time of drug initiation, have no structural heart disease, and are receiving concurrent AV nodal blockade. 2

• The first dose should ideally be given in a monitored setting to establish safety, particularly for patients with sustained ventricular tachycardia or any cardiac status concerns 1
• For the "pill-in-the-pocket" approach, safety must first be verified in a monitored hospital setting before allowing out-of-hospital use 2

Common Clinical Pitfalls

• Never initiate flecainide without concurrent AV nodal blockade unless the patient has documented AV node conduction impairment, as conversion to atrial flutter with 1:1 conduction can cause dangerously rapid ventricular rates 2, 3
• Do not use loading doses in patients with sustained ventricular tachycardia, as higher initial doses and rapid dosage adjustments increase proarrhythmic events and congestive heart failure risk 1
• Avoid flecainide in any patient with structural heart disease, even mild left ventricular dysfunction, as this represents the primary safety concern from CAST trial data 4, 5
• Check renal function before each dose adjustment, as flecainide requires dose reduction in renal impairment and small changes in dose can lead to disproportionate increases in plasma levels 1