What are the side effects of flecainide?

Side Effects of Flecainide

Flecainide has significant potential for serious cardiac side effects including proarrhythmic events, which can lead to ventricular tachycardia, ventricular fibrillation, and cardiac arrest, especially in patients with structural heart disease. 1

Cardiac Side Effects

Proarrhythmic Effects

• Ventricular proarrhythmia occurs in 7-8% of patients, with higher incidence in those with serious ventricular tachycardia and reduced myocardial function 2
• 80% of proarrhythmic events occur within the first 14 days of therapy in patients treated for sustained ventricular tachycardia 1
• Can cause new or worsened supraventricular or ventricular arrhythmias 1
• Risk is significantly higher in patients with:
  • Previous myocardial infarction 3
  • Structural heart disease 4
  • Reduced ejection fraction 1
  • History of cardiac arrest 1

Conduction Abnormalities

• QRS prolongation 4
• PR interval prolongation 4
• Second-degree (0.5%) or third-degree (0.4%) AV block 1
• Sinus bradycardia, sinus pause, or sinus arrest (approximately 1.2% of patients) 1

Cardiac Function

• Negative inotropic effects that can worsen heart failure 4
• New or worsened congestive heart failure in:
  • 6.3% of patients with PVCs, non-sustained or sustained VT
  • 9.1% of patients with sustained VT
  • 0.4% of patients with supraventricular arrhythmias 1

Non-Cardiac Side Effects

Neurological

• Dizziness (18.9% of patients) - most common non-cardiac side effect 1
• Headache (9.6%) 1
• Visual disturbances (15.9%) including blurred vision, difficulty focusing, spots before eyes 1, 5
• Tremor (4.7%) 1
• Less common: paresthesia, hypoesthesia, ataxia, syncope, vertigo, tinnitus 1

Gastrointestinal

• Nausea (8.9%) 1
• Constipation (4.4%) 1
• Abdominal pain (3.3%) 1
• Less common: vomiting, diarrhea, dyspepsia, anorexia 1

Respiratory

• Dyspnea (10.3%) 1
• Rare: pneumonitis/pulmonary infiltration with chronic use 1

General

• Fatigue (7.7%) 1
• Asthenia (4.9%) 1
• Chest pain (5.4%) 1
• Edema (3.5%) 1

Rare but Serious Side Effects

• Hepatic dysfunction including cholestasis and hepatic failure 1
• Blood dyscrasias (extremely rare) 1
• Leukopenia, granulocytopenia, thrombocytopenia (less than 1%) 1

Risk Factors for Flecainide Toxicity

Patients at higher risk for flecainide toxicity include those with:

• Renal impairment (flecainide is primarily eliminated through the kidneys) 4, 6
• Hepatic dysfunction 4
• Heart failure 4
• Concomitant amiodarone therapy (requires 50% dose reduction) 4
• Electrolyte disturbances 4, 6
• Female gender (higher risk for class IC proarrhythmic toxicity) 4
• Brugada syndrome (contraindicated) 4

Monitoring Recommendations

• Baseline ECG before initiation of therapy 4
• Follow-up ECG after 3-5 days of therapy, at each dose change, and at regular intervals 4
• Trough plasma levels should be maintained between 0.2-1.0 mcg/mL 4
• Levels above 0.7-1.0 mcg/mL require close monitoring 4
• Plasma level monitoring is particularly important in patients with severe renal impairment, hepatic disease, or heart failure 4

Contraindications

Flecainide should not be used in patients with:

• Structural heart disease or coronary artery disease 4
• Significant ventricular dysfunction 4
• Cardiogenic shock 4
• Sinus or AV conduction disease (without pacemaker) 4
• Brugada syndrome 4
• Previous myocardial infarction 3

Management of Toxicity

For flecainide toxicity, treatment includes:

• Supportive care with continuous cardiac monitoring 4
• Maintaining adequate oxygenation 4
• Correcting electrolyte abnormalities 4, 6
• Sodium bicarbonate therapy (initial bolus of 1-2 mEq/kg IV followed by continuous infusion) 4
• Calcium gluconate (1-2 g IV) to help stabilize myocardial cell membranes 4

Flecainide toxicity is a serious condition that can lead to cardiogenic shock if not recognized and treated promptly 6. Careful patient selection and monitoring are essential to ensure that the benefits of treatment outweigh the potential risks 5.