What are the effects of Flecainide (Anti-arrhythmic medication) toxicity?

From the Guidelines

Flecainide toxicity is a life-threatening condition that requires immediate discontinuation of the medication and emergency medical attention. Flecainide toxicity can occur due to various factors, including overdosing, kidney or liver dysfunction, heart failure, electrolyte abnormalities, and drug interactions with CYP2D6 inhibitors like amiodarone or certain SSRIs 1. The symptoms of flecainide toxicity include visual disturbances, dizziness, confusion, bradycardia, hypotension, widened QRS complex on ECG, and in severe cases, ventricular arrhythmias or cardiac arrest. Treatment involves supportive care, sodium bicarbonate administration (typically 1-2 mEq/kg IV bolus, followed by infusion), and possibly temporary cardiac pacing for bradyarrhythmias 1. Some key points to consider when managing flecainide toxicity include:

• Discontinuing the medication immediately
• Seeking emergency care
• Administering sodium bicarbonate
• Considering temporary cardiac pacing for bradyarrhythmias
• Avoiding interacting medications when possible
• Regular monitoring of ECG and drug levels
• Careful dosing (typically 50-200 mg twice daily for adults, with lower doses for those with renal impairment) 1. It is essential to prioritize the patient's morbidity, mortality, and quality of life when managing flecainide toxicity, and to take a cautious approach when prescribing flecainide, especially in patients with pre-existing heart conditions or those taking interacting medications 1.

From the FDA Drug Label

Flecainide acetate, like other antiarrhythmic agents, can cause new or worsened supraventricular or ventricular arrhythmias. In studies of ventricular arrhythmia patients treated with flecainide acetate, three-fourths of proarrhythmic events were new or worsened ventricular tachyarrhythmias, the remainder being increased frequency of PVCs or new supraventricular arrhythmias In patients treated with flecainide for sustained ventricular tachycardia, 80% (51/64) of proarrhythmic events occurred within 14 days of the onset of therapy The incidence of proarrhythmic events was 13% when dosage was initiated at 200 mg/day with slow upward titration, and did not exceed 300 mg/day in most patients In early studies in patients with sustained VT utilizing a higher initial dose (400 mg/day) the incidence of proarrhythmic events was 26%; moreover, in about 10% of the patients treated proarrhythmic events resulted in death, despite prompt medical attention.

Flecainide toxicity can manifest as proarrhythmic effects, including new or worsened supraventricular or ventricular arrhythmias. The risk of proarrhythmia is higher in patients with sustained ventricular tachycardia and underlying heart disease. Key points to consider:

• Proarrhythmic events can occur in up to 13% of patients treated with flecainide for sustained VT
• Mortality due to proarrhythmic events can occur, especially with higher initial doses (400 mg/day)
• Monitoring and slow upward titration of the dose are crucial to minimize the risk of proarrhythmia
• Cardiac arrest and unresuscitatable VT or ventricular fibrillation have been reported in some patients treated with flecainide 2 2 2

From the Research

Flecainide Toxicity Overview

• Flecainide is a class Ic antidysrhythmic agent used to prevent and treat both ventricular and supraventricular tachycardias, including atrial fibrillation, atrioventricular nodal re-entrant tachycardia, and Wolff-Parkinson-White syndrome 3.
• Flecainide can cause serious side effects, including cardiac arrest, dysrhythmias, and heart failure 3, 4.

Clinical Presentation and Diagnosis

• The presenting signs and symptoms of flecainide toxicity are not familiar to most clinicians, and its diagnosis can be difficult, as the flecainide serum level may take days to result 3.
• Flecainide toxicity can manifest as a bizarre right or left bundle branch block, sometimes with a northwest axis, and can easily be mistaken for ventricular tachycardia leading to inappropriate therapy 5.
• Clinical suspicion, clinical presentation, and electrocardiogram can help clinicians diagnose flecainide toxicity 6.
• The duration of the QRS interval is prognostic, with mortality and the requirement for mechanical circulatory support being more common in patients with a QRS > 200 ms 5.

Treatment and Management

• Treatment can be lifesaving if initiated promptly, and sodium bicarbonate, lipid emulsion therapy, and extracorporeal life support have been used in this setting 6, 4.
• Amiodarone and lidocaine can be used for the management of wide QRS complex tachycardias in hemodynamically stable patients with flecainide toxicity 6.
• Early recognition is crucial, as delayed diagnosis and treatment can be fatal 4.

Electrocardiographic Patterns

• In patients with flecainide toxicity and QRS duration ≤ 200 ms, the ECGs were more likely to show RBBB, visible P waves, and shorter QT and QTc intervals 5.
• With QRS duration > 200 ms, the ECGs were more likely to show LBBB, loss of P waves, a northwest axis, and longer QT and QTc intervals 5.