Flecainide - Drug Monograph

Introduction

Flecainide acetate is a class IC antiarrhythmic agent used primarily for the management of certain cardiac arrhythmias. First approved by the FDA in 1985, it remains an important therapeutic option for specific rhythm disorders, particularly in patients without structural heart disease. Flecainide is notable for its potent sodium channel blocking properties and is available in both oral and intravenous formulations.

Mechanism of Action

Flecainide exerts its antiarrhythmic effects primarily through potent blockade of cardiac sodium channels (fast inward sodium current). This action:

• Decreases the rate of rise of phase 0 of the cardiac action potential
• Prolongs the effective refractory period in the His-Purkinje system
• Slows conduction velocity throughout the myocardium
• Moderately inhibits potassium channels, prolonging action potential duration

These electrophysiological effects make flecainide particularly effective for suppressing abnormal automaticity and interrupting reentrant circuits, especially in the atria.

Indications

• Prevention of paroxysmal supraventricular tachycardias (PSVT), including atrioventricular nodal reentrant tachycardia and atrioventricular reentrant tachycardia
• Prevention of paroxysmal atrial fibrillation/flutter in patients without structural heart disease

• Pharmacological cardioversion of recent-onset atrial fibrillation
• Ventricular arrhythmias (with caution and only in selected patients without structural heart disease)
• Catecholaminergic polymorphic ventricular tachycardia (CPVT)

Dosage and Administration

• Initial dose: 50 mg every 12 hours
• May increase in increments of 50 mg twice daily every 4 days
• Maximum recommended dose: 300 mg/day (150 mg twice daily)

• Loading dose: 2 mg/kg over 10-30 minutes
• Maintenance infusion: 1.5 mg/kg/hour for first hour, then 0.1-0.25 mg/kg/hour

• Renal impairment: Reduce dose by 25-50% for CrCl <35 mL/min
• Hepatic impairment: Use with caution and consider dose reduction
• Elderly: Start with lower initial doses (25 mg twice daily)
• Pediatric use: Limited data; consult specialist guidance

Pharmacokinetics

Contraindications

• Second- or third-degree AV block without a pacemaker
• Right bundle branch block with left anterior or posterior hemiblock (bifascicular block)
• Recent myocardial infarction
• Cardiogenic shock
• Structural heart disease with reduced ejection fraction (<40%)
• Hypersensitivity to flecainide or any component of the formulation
• Concomitant use with ritonavir or other strong CYP3A4 inhibitors

Warnings and Precautions

• Proarrhythmic effects: May cause new or worsened arrhythmias (1-7% of patients)
• Atrial flutter with 1:1 conduction: May organize atrial fibrillation to flutter with rapid ventricular response
• Heart failure: May worsen pre-existing heart failure due to negative inotropic effects
• Conduction abnormalities: May cause sinus node dysfunction or AV block
• CYP2D6 poor metabolizers: Increased drug exposure and toxicity risk
• Electrolyte imbalances: Hypokalemia or hyperkalemia may enhance proarrhythmic risk
• Pregnancy: Category C; use only if potential benefit justifies potential risk
• Lactation: Excreted in breast milk; consider alternative feeding options

Drug Interactions

• Antiarrhythmics: Increased proarrhythmic risk with other class I/III agents
• Beta-blockers: Additive negative inotropic and chronotropic effects
• Digoxin: Increases digoxin levels by 15-25%
• Calcium channel blockers: Additive effects on AV conduction
• CYP2D6 inhibitors: Paroxetine, fluoxetine, quinidine (increased flecainide levels)
• Amiodarone: Increases flecainide levels by 30-60%
• Ritonavir: Contraindicated due to significant interaction

Adverse Effects

• Dizziness (19%)
• Visual disturbances (blurred vision, difficulty focusing) (16%)
• Dyspnea (10%)
• Headache (9%)
• Nausea (8%)
• Fatigue (7%)

• Proarrhythmia (new or worsened ventricular arrhythmias)
• Heart failure exacerbation
• Conduction abnormalities (heart block, bundle branch block)
• Increased mortality in high-risk populations
• Hepatotoxicity
• Blood dyscrasias (rare)

Monitoring Parameters

• ECG (evaluate PR, QRS, QT intervals)
• Cardiac function (echocardiogram if not recently performed)
• Renal and hepatic function
• Electrolytes (potassium, magnesium)
• Pregnancy test if appropriate

• ECG at dose changes and periodically during therapy
• Monitor for QRS widening (>25% increase requires dose reduction)
• Regular assessment of cardiac symptoms and arrhythmia control
• Renal function every 6-12 months
• Therapeutic drug monitoring (target range 0.2-1.0 μg/mL)

Patient Education

• Take medication exactly as prescribed at regular intervals
• Do not stop abruptly without medical supervision
• Report any symptoms of dizziness, visual changes, palpitations, or shortness of breath
• Maintain regular follow-up appointments for ECG monitoring
• Inform all healthcare providers about flecainide use
• Avoid grapefruit juice (may affect metabolism)
• Be aware of potential proarrhythmic risks
• Use caution when driving or operating machinery until effects are known
• Report any signs of infection (fever, sore throat) due to rare blood dyscrasia risk

References

1. FDA Prescribing Information: Tambocor (flecainide acetate) 2. January CT, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. J Am Coll Cardiol 2019;74:104-132 3. Alboni P, et al. Efficacy and safety of outpatient flecainide for cardioversion of atrial fibrillation. Am J Cardiol 2016;117:406-409 4. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med 1989;321:406-412 5. Roden DM. Antiarrhythmic drugs: from mechanisms to clinical practice. Heart Rhythm 2020;17:1453-1465 6. Lexicomp Online, Flecainide monograph. Wolters Kluwer Clinical Drug Information 7. Micromedex Solutions, Flecainide drug monograph. IBM Watson Health