Flecainide Dosing for Arrhythmias
Initial Dosing Strategy
For supraventricular arrhythmias including atrial fibrillation and paroxysmal supraventricular tachycardia, start flecainide at 50 mg every 12 hours (100 mg/day total), then increase by 50 mg twice daily every 4 days as needed, up to a maximum of 150 mg every 12 hours (300 mg/day total). 1, 2, 3
For sustained ventricular tachycardia, the starting dose is higher at 100 mg every 12 hours, with the same titration schedule of 50 mg twice daily increments every 4 days. 3 The maximum dose for ventricular tachycardia is 400 mg/day, though most patients respond to 300 mg/day or less. 3
The 4-day interval between dose increases is critical because flecainide has a long half-life (12-27 hours), and steady-state plasma levels may not be achieved until 3-5 days of therapy at a given dose. 3 Increasing doses more frequently increases the risk of proarrhythmic events and heart failure, particularly during the first few days. 3
Acute Cardioversion Dosing
For acute conversion of atrial fibrillation, use a single oral dose of 200-300 mg ("pill-in-the-pocket" approach) after safety has been demonstrated in a monitored setting, or intravenous administration of 1.5-3.0 mg/kg over 10-20 minutes. 1, 2
The oral loading approach is reasonable for self-administration once safety has been established, but initial conversion should occur under medical supervision. 1, 2
Dose Titration and Maintenance
Increase the dose in 50 mg twice daily increments every 4 days until arrhythmia control is achieved. 2, 3 For atrial fibrillation patients, increasing from 50 mg to 100 mg twice daily provides substantial improvement in efficacy without significantly increasing adverse effects. 3
Once adequate arrhythmia control is achieved, consider reducing the dose to minimize side effects or conduction effects, then re-evaluate efficacy at the lower dose. 3
The therapeutic plasma trough level range is 0.2-1.0 mcg/mL, with most successfully treated patients having levels between 0.2-1.0 mcg/mL. 2, 3 Levels exceeding 1.0 mcg/mL increase the probability of adverse cardiac effects. 3
Special Population Dosing
In patients with severe renal impairment (creatinine clearance ≤35 mL/min/1.73 m²), start at 100 mg once daily (or 50 mg twice daily) with mandatory frequent plasma level monitoring. 3
For less severe renal disease, start at 100 mg every 12 hours with plasma level monitoring during dose adjustment. 3 Dosage increases should be made very cautiously after plasma levels have plateaued (more than 4 days), as it may take longer to reach steady state. 3
When flecainide is given with amiodarone, reduce the usual flecainide dose by 50% and monitor closely, with plasma level monitoring strongly recommended. 3
Critical Monitoring Requirements
Obtain a baseline ECG measuring PR interval, QRS duration, and QT interval before starting therapy. 2, 4 During dose titration, obtain an ECG after each dose change and calculate the percentage change in QRS duration from baseline. 4
A QRS duration increase of ≥25% compared to baseline is the critical threshold signaling potential proarrhythmia risk and mandates either dose reduction or drug discontinuation. 4
PR interval prolongation is an expected therapeutic effect of flecainide's sodium channel blockade and does not require discontinuation in patients with normal cardiac conduction. 4 Focus monitoring on QRS duration changes, not PR interval changes. 4
Monitor trough plasma levels periodically, targeting 0.2-1.0 mcg/mL. 2, 3 Plasma level monitoring is required in severe renal or hepatic disease, strongly recommended with concurrent amiodarone, and helpful in heart failure and moderate renal disease. 3
Absolute Contraindications
Never use flecainide in patients with structural heart disease (coronary artery disease, heart failure, significant left ventricular dysfunction), as this is associated with increased mortality demonstrated in the CAST trial. 2
Other absolute contraindications include sinus or AV node dysfunction, Brugada syndrome, and atrial flutter without concomitant AV nodal blocking therapy. 2
Critical Pitfalls to Avoid
Always co-administer an AV nodal blocking agent (beta-blocker, calcium channel blocker, or digoxin) to prevent atrial flutter with 1:1 AV conduction, a potentially life-threatening complication. 2, 4
Flecainide is metabolized by CYP2D6, which is genetically absent in 7-10% of the population and can be inhibited by quinidine, fluoxetine, and tricyclic antidepressants. 2 These interactions can dramatically increase plasma concentrations, requiring dose adjustment and plasma level monitoring.
For patients on digoxin, reduce the digoxin dose when initiating flecainide, as digoxin levels typically rise. 4 Similarly, monitor INR closely and anticipate reducing warfarin dose with concurrent flecainide. 4
Initiate therapy in-hospital for patients with sustained ventricular tachycardia, though outpatient initiation is acceptable for supraventricular arrhythmias in selected patients without structural heart disease or conduction abnormalities. 2, 4