What are the typical dosing regimens of the anti‑arrhythmic flecainide in adults for supraventricular tachyarrhythmias and ventricular ectopy, including oral and intravenous administration and adjustments for moderate renal impairment?

Flecainide Dosing for Supraventricular Arrhythmias and Ventricular Ectopy

For supraventricular tachyarrhythmias (PSVT, paroxysmal atrial fibrillation), start flecainide at 50 mg every 12 hours orally, increasing by 50 mg twice daily every 4 days as needed, up to a maximum of 300 mg/day (150 mg twice daily). 1, 2

Oral Dosing Regimens

Supraventricular Arrhythmias (PSVT, Paroxysmal AF)

• Initial dose: 50 mg every 12 hours 1, 2
• Titration: Increase by 50 mg twice daily every 4 days until efficacy is achieved 2
• Maximum dose: 300 mg/day (150 mg twice daily) 1, 2
• Patients may experience substantial efficacy improvement when increasing from 50 mg to 100 mg twice daily 2
• Some patients requiring more frequent dosing may use 8-hour intervals instead of 12-hour intervals 2

Sustained Ventricular Tachycardia

• Initial dose: 100 mg every 12 hours 2
• Titration: Increase by 50 mg twice daily every 4 days 2
• Typical effective dose: Most patients respond to 150 mg every 12 hours (300 mg/day) 2
• Maximum dose: 400 mg/day 2
• Critical warning: Higher initial doses and rapid titration increase proarrhythmic events and congestive heart failure risk, particularly in the first few days—therefore loading doses are not recommended 2
• Must be initiated in-hospital with rhythm monitoring 2

Intravenous Dosing for Acute Cardioversion

For pharmacological cardioversion of atrial fibrillation or atrial flutter, administer flecainide 1.5 to 3.0 mg/kg intravenously over 10 to 20 minutes. 1

• The IV route provides earlier conversion compared to oral loading, though both are equally efficacious overall 3
• IV administration should be reserved for monitored settings 1

Single Oral Loading Dose ("Pill-in-the-Pocket")

• Dose: 200 to 300 mg as a single oral dose 1
• Timing of effect: Conversion occurs in 57-68% of patients at 2-4 hours and 75-91% at 8 hours 3
• Mean conversion time: 110-190 minutes depending on observation duration 3
• This approach is reasonable for terminating AF out of hospital once safety has been demonstrated in a monitored setting 1
• Mandatory co-administration: A beta blocker or nondihydropyridine calcium channel antagonist should be given ≥30 minutes before the Class IC agent to prevent atrial flutter with rapid 1:1 AV conduction 1

Dose Adjustments for Renal Impairment

In moderate renal impairment (creatinine clearance 35 mL/min/1.73 m² or less), reduce the initial flecainide dose and titrate more cautiously, as 30% of the drug is excreted unchanged renally. 2, 4, 5

• Flecainide elimination is markedly slower in end-stage renal disease 5
• Plasma half-life increases from 13-16 hours in healthy subjects to 20 hours in cardiac patients, and even longer in renal failure 5
• Hemodialysis does not effectively remove unchanged flecainide 5
• The FDA label specifically notes that severe renal impairment requires dosage reduction 2

Critical Pharmacokinetic Considerations

• Half-life: 12-27 hours in patients, requiring 3-5 days to reach steady state 2
• Dosing frequency: Because of the long half-life, increases should occur no more frequently than every 4 days 2
• Therapeutic plasma levels: 200-500 ng/mL in most patients; some may require up to 800 ng/mL 2
• Plasma trough levels (obtained <1 hour pre-dose) should be monitored at steady state 2

Absolute Contraindications to Flecainide

Flecainide is absolutely contraindicated in patients with structural heart disease, including coronary artery disease, heart failure, or reduced left ventricular ejection fraction. 1, 6

• The CAST trial demonstrated increased mortality with Class IC agents in patients with structural heart disease 7
• Also contraindicated in sinus or AV conduction disease without a pacemaker, cardiogenic shock, and Brugada syndrome 1
• Avoid in atrial flutter unless concomitant AV nodal blockade is provided to prevent 1:1 AV conduction 1

Monitoring Requirements During Therapy

ECG Monitoring

• Baseline ECG required before initiation to measure PR interval, QRS duration, and QT interval 6
• Critical threshold: QRS widening ≥25% from baseline mandates dose reduction or discontinuation due to proarrhythmic risk 6
• Obtain ECG after each dose change during titration 6
• Weekly ECG monitoring recommended during dose adjustments 6

Laboratory Monitoring

• Baseline and periodic liver function tests (SGPT/ALT) 6
• Serum electrolytes (potassium and magnesium) must be normal before initiation 6
• Periodic trough plasma levels with target range 0.2-1.0 mcg/mL 6

Drug Interaction Monitoring

• Reduce digoxin dose by 30-50% when co-administering flecainide, as digoxin levels typically rise 1, 6
• Monitor INR closely with warfarin co-administration 6
• CYP2D6 inhibitors (amiodarone, ritonavir, saquinavir) increase flecainide levels significantly 1, 6

Common Pitfalls to Avoid

• Do not use loading doses in sustained ventricular tachycardia, as this increases proarrhythmic events 2
• Do not initiate dofetilide out of hospital, but flecainide may be used as "pill-in-the-pocket" after in-hospital safety demonstration 1
• Do not ignore QRS widening: The 25% threshold is the critical safety marker, not PR prolongation (which is expected and therapeutic) 6
• Do not use in chronic atrial fibrillation with structural heart disease: This population has the highest rate of cardiac adverse events (5/17 patients in one trial) 7
• Small dose changes in children can lead to disproportionate plasma level increases—monitor closely 2