Should I be concerned about side effects of flecainide?

Should You Be Concerned About Side Effects of Flecainide?

Yes, you should be appropriately concerned about flecainide's side effects, particularly the serious cardiac risks including proarrhythmia, conduction abnormalities, and worsening heart failure, but these risks are largely confined to specific high-risk populations—especially those with structural heart disease, coronary artery disease, or reduced left ventricular function. 1, 2, 3

Understanding the Serious Cardiac Risks

Proarrhythmia (New or Worsened Arrhythmias)

• The most concerning risk is proarrhythmia—flecainide can paradoxically cause new or worsened dangerous heart rhythms, including ventricular tachycardia and ventricular fibrillation. 3
• In patients with sustained ventricular tachycardia, 80% of proarrhythmic events occurred within the first 14 days of therapy. 3
• The FDA label reports that 13% of patients with sustained ventricular tachycardia experienced new or exacerbated ventricular arrhythmias. 3
• Flecainide can convert atrial fibrillation to atrial flutter with rapid 1:1 atrioventricular conduction, a potentially life-threatening complication. 1, 2

Conduction Abnormalities

• QRS widening of ≥25% from baseline is the critical warning sign of toxicity and requires immediate dose reduction or discontinuation. 2, 4
• Second-degree (0.5%) or third-degree (0.4%) heart block can occur. 3
• Sinus bradycardia, sinus pause, or sinus arrest occurs in approximately 1.2% of patients. 3

Heart Failure Worsening

• New or worsened congestive heart failure occurred in 6.3% of patients with ventricular arrhythmias and 9.1% of those with sustained ventricular tachycardia. 3
• This risk is particularly elevated in patients with pre-existing ventricular dysfunction. 1

Who Is at Highest Risk?

Absolute Contraindications (Do NOT Use Flecainide)

• Patients with structural heart disease, including coronary artery disease, prior myocardial infarction, or heart failure. 1, 2, 4
• Patients with reduced left ventricular ejection fraction (LVEF <30% or significant dysfunction). 4
• Patients with sinus or AV conduction disease without a pacemaker. 1
• Patients with Brugada syndrome. 1
• In adult congenital heart disease patients with significant ventricular dysfunction, flecainide should not be used due to cardiac arrest risk. 1

High-Risk Situations Requiring Extreme Caution

• Pre-existing conduction abnormalities (sick sinus syndrome, bundle branch block). 4
• Renal dysfunction (flecainide accumulates and can reach toxic levels). 1, 5
• Hepatic dysfunction. 1
• Atrial flutter without concomitant AV nodal blocking therapy. 1

Common Non-Cardiac Side Effects (Generally Mild and Tolerable)

Most Frequent Side Effects

• Dizziness (18.9% of patients)—includes lightheadedness, faintness, unsteadiness, near syncope. 3, 6
• Visual disturbances (15.9%)—includes blurred vision, difficulty focusing, spots before eyes. 3, 6
• Dyspnea (10.3%). 3
• Headache (9.6%). 3
• Nausea (8.9%). 3
• Fatigue (7.7%). 3

Less Common Side Effects

• Tremor, constipation, edema, abdominal pain (3-5% each). 3
• Anxiety, insomnia, depression, paresthesia, ataxia. 3
• These non-cardiac effects are almost all mild, transient, and tolerable, rarely requiring discontinuation. 6

Critical Monitoring Requirements

Before Starting Flecainide

• Baseline 12-lead ECG to measure PR interval, QRS duration, and QT interval is mandatory. 4
• Echocardiogram to exclude structural heart disease and assess LVEF. 4
• Baseline liver function tests and serum electrolytes (potassium, magnesium). 4

During Therapy

• Regular ECG monitoring, especially during the first 14 days and after any dose change. 2, 4, 3
• Calculate QRS duration change from baseline—if ≥25% increase occurs, reduce dose or stop the drug immediately. 2, 4
• Weekly ECGs during dose titration. 4
• Periodic monitoring of trough plasma levels (therapeutic range 0.2-1.0 mcg/mL; toxic >1.5 mcg/mL). 4, 5

Rare but Serious Organ Toxicity

• Rare reports of hepatic dysfunction, including cholestasis and hepatic failure. 3
• Extremely rare reports of blood dyscrasias (leukopenia, granulocytopenia, thrombocytopenia). 3
• Rare pneumonitis/pulmonary infiltration with chronic use. 3
• Discontinue flecainide if unexplained jaundice, signs of hepatic dysfunction, or blood dyscrasias develop. 3

Drug Interactions to Monitor

• Digoxin levels typically rise with flecainide—reduce digoxin dose by 30-50%. 1, 4
• Amiodarone increases flecainide levels—monitor closely. 1
• CYP2D6 inhibitors increase flecainide concentrations. 4
• Warfarin INR may increase—monitor closely and anticipate dose reduction. 4

The Bottom Line on Safety

Flecainide has a good safety record and low incidence of adverse effects in appropriately selected patients without structural heart disease. 6 The key distinction is:

• In patients WITHOUT structural heart disease, coronary disease, or heart failure: flecainide is generally safe with careful monitoring, and most side effects are mild and manageable. 1, 6
• In patients WITH structural heart disease, prior MI, or reduced LVEF: flecainide is contraindicated due to unacceptable mortality risk. 1, 2, 4

The critical safety measure is proper patient selection before starting the drug—this requires cardiology evaluation to exclude contraindications. 2 Once appropriately selected patients are on therapy, the most important monitoring parameter is QRS duration on ECG, not the common mild side effects like dizziness or visual changes. 2, 4