Flecainide: Key Considerations for Arrhythmia Management
Classification and Mechanism
Flecainide is a Class IC antiarrhythmic drug that blocks cardiac sodium channels (Nav1.5), slowing conduction through the heart and prolonging both the PR interval and QRS complex. 1, 2
Primary Indications
FDA-Approved Uses
- Paroxysmal supraventricular tachycardias (PSVT) including AVNRT, AVRT, and other SVTs in patients without structural heart disease 1
- Paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms 1
- Documented life-threatening ventricular arrhythmias (sustained VT) - initiation must occur in hospital 1
Evidence-Based Efficacy
- For AVNRT: Flecainide demonstrates superior long-term efficacy compared to verapamil, with 30% achieving complete symptomatic suppression versus 13% with verapamil 3
- For AVRT: Oral flecainide (200-300 mg/day) rendered sustained tachycardia non-inducible in 85% (17/20) of patients 3
- For PSVT: Flecainide showed superiority over placebo with only 24% recurrence rate versus 85% on placebo in controlled trials 3
- Combination with beta-blockers increases efficacy to >90% for abolition of symptomatic tachycardia 3
Route and Dosage
Oral Administration
- Initial dose: 100 mg twice daily (every 12 hours) 1
- Titration: May increase by 50 mg twice daily every 4 days 1
- Maximum dose: 200 mg twice daily (400 mg/day total) 1
- Therapeutic plasma levels: 0.2-1.0 mcg/mL (200-1000 ng/mL) 1
- Some patients may require 8-hour dosing intervals if inadequately controlled 1
Pediatric Dosing
- <6 months: 50 mg/M² body surface area daily, divided into 2-3 doses 1
- >6 months: 100 mg/M² daily initially, maximum 200 mg/M² daily 1
- Therapeutic levels in children: 200-500 ng/mL (may require up to 800 ng/mL) 1
- Requires direct supervision by pediatric cardiologist 1
Renal Impairment Adjustments
- Severe renal impairment (CrCl ≤35 mL/min/1.73m²): 100 mg once daily initially with mandatory plasma level monitoring 1
- Moderate renal disease: 100 mg every 12 hours with recommended plasma level monitoring 1
Critical Contraindications and Precautions
Absolute 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
- Recent myocardial infarction 1
- Structural heart disease of any kind 3
- Ischemic heart disease 3
- Chronic atrial fibrillation (not adequately studied and not recommended) 1
High-Risk Populations Requiring Extreme Caution
- Congestive heart failure or myocardial dysfunction - use cautiously with close monitoring 1
- Pre-existing conduction disorders - 52% of patients in one study had baseline conduction abnormalities 4
- Left ventricular ejection fraction ≤30% - associated with higher adverse event rates 4
Special Monitoring Requirements
Plasma level monitoring is mandatory in:
- Severe renal failure 1
- Severe hepatic disease 1
- Concurrent amiodarone therapy (reduce flecainide dose by 50%) 1
- Congestive heart failure 1
- Moderate renal disease 1
- Pediatric patients (trough levels before dose adjustments) 1
Adverse Reactions and Proarrhythmic Effects
Cardiac Adverse Effects
The most serious concern is proarrhythmia, particularly in patients with structural heart disease or when plasma levels exceed 1.0 mcg/mL 1
- Proarrhythmic events: New or worsened ventricular arrhythmias, including non-sustained VT 5, 6
- New or worsened congestive heart failure (occurred in 7 patients in one multicenter trial) 5
- Conduction disturbances: Third-degree heart block, sinus pauses 5, 4
- QRS widening and PR prolongation 1, 2
- Aggravation of arrhythmia occurred in 10/94 patients (11%) with ventricular tachycardia 4
Non-Cardiac Adverse Effects
Most common non-cardiac side effects (reported in 56-67% of patients): 5
- Abnormal vision (most frequent CNS effect) 5
- Dizziness 5
- Headaches 5
- CNS side effects led to discontinuation in 5% of patients without structural heart disease 3
Discontinuation Rates
- 7.6% discontinued due to suboptimal clinical response 3
- 19-24% discontinued due to adverse effects in comparative trials 3
Critical Drug Interactions
Amiodarone
When flecainide is given with amiodarone, reduce flecainide dose by 50% and monitor plasma levels closely 1
Beta-Blockers
Combination with beta-blockers is recommended to:
- Enhance efficacy (>90% success rate for AVRT) 3
- Reduce risk of 1:1 AV conduction if atrial flutter develops 3
Isoproterenol
Isoproterenol partially reverses the electrophysiological effects of flecainide 3
Drugs to Avoid in Pre-Excited Tachycardias
Adenosine should be used with caution as it may precipitate atrial fibrillation with rapid ventricular rate in pre-excited tachycardias 3
Essential Assessments
Before Initiation
- Exclude structural heart disease (echocardiography mandatory) 3
- Exclude ischemic heart disease 3
- Baseline ECG: Document PR interval, QRS duration, QTc 1
- Renal function assessment (creatinine clearance) 1
- Hepatic function assessment 1
- Baseline electrophysiology study may be considered for high-risk patients 1
During Treatment Monitoring
- Trough plasma levels (drawn <1 hour pre-dose) at steady state (after ≥5 doses) 1
- 12-lead ECG monitoring for QRS widening and PR prolongation 1
- In pediatric patients: Plasma levels and ECG at every dose change and at each follow-up visit for first year 1
- 24-hour Holter monitoring to detect subclinical ventricular arrhythmias 6
- Monitor for signs of heart failure 1
Frequency of Monitoring
- Plasma levels should plateau after >4 days before dosage adjustments 1
- In renal impairment, may take longer than 4 days to reach steady state 1
- Probability of adverse cardiac effects increases with trough levels >1.0 mcg/mL 1
Hemodynamic and Multi-System Effects
Cardiovascular System
- Negative inotropic effects: Can precipitate or worsen heart failure 1, 5
- Slowed cardiac conduction: PR prolongation, QRS widening 1, 2
- Increased accessory pathway refractoriness (both anterograde and retrograde) 2
- Risk of 1:1 atrial flutter conduction if not combined with AV nodal blocking agents 3
Central Nervous System
Visual disturbances are the most characteristic CNS effect, along with dizziness and headache 5
Mortality Considerations
In the CAST trial context, flecainide should not be used in post-MI patients or those with structural heart disease due to increased mortality risk 1, 5
- Sudden cardiac death occurred in 6/94 patients (6.4%) in one ventricular tachycardia study, though causality unclear 4
- One death in CAF group considered unrelated to flecainide 5
Clinical Pitfalls and How to Avoid Them
Common Errors
- Using flecainide in patients with unrecognized structural heart disease - Always obtain echocardiography before initiation 3
- Failure to monitor plasma levels in high-risk populations - Mandatory in renal/hepatic disease and with amiodarone 1
- Not combining with beta-blockers in AVRT/AVNRT - Reduces efficacy and increases atrial flutter risk 3
- Inadequate follow-up in subjectively improved patients - Ventricular arrhythmias may develop despite symptom improvement 6
- Using in chronic atrial fibrillation - Not adequately studied and not recommended 1
Guideline-Based Treatment Algorithm
According to ACC/AHA/HRS 2015 guidelines: 3
First-line for AVNRT/AVRT: Beta-blockers, diltiazem, or verapamil 3
Second-line (Class IIa recommendation): Flecainide or propafenone ONLY if:
- No structural heart disease confirmed
- No ischemic heart disease
- First-line agents ineffective or contraindicated
- Patient not candidate for or refuses catheter ablation 3
For pre-excited tachycardias: Flecainide, ibutilide, or procainamide preferred over AV nodal blockers 3