Flecainide - Warnings and Precautions

WARNINGS Mortality Flecainide acetate was included in the National Heart Lung and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than six days but less than two years previously.

An excessive mortality or non-fatal cardiac arrest rate was seen in patients treated with flecainide acetate compared with that seen in patients assigned to a carefully matched placebo-treated group.

This rate was 16/315 (5.1%) for flecainide acetate and 7/309 (2.3%) for the matched placebo.

The average duration of treatment with flecainide acetate in this study was ten months.

The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) is uncertain, but at present, it is prudent to consider the risks of Class IC agents (including flecainide acetate), coupled with the lack of any evidence of improved survival, generally unacceptable in patients without life-threatening ventricular arrhythmias, even if the patients are experiencing unpleasant, but not life-threatening, symptoms or signs.

Ventricular Pro-Arrhythmic Effects in Patients with Atrial Fibrillation/Flutter A review of the world literature revealed reports of 568 patients treated with oral flecainide acetate for paroxysmal atrial fibrillation/flutter (PAF).

Ventricular tachycardia was experienced in 0.4% (2/568) of these patients.

Of 19 patients in the literature with chronic atrial fibrillation (CAF), 10.5% experienced VT or VF.

FLECAINIDE IS NOT RECOMMENDED FOR USE IN PATIENTS WITH CHRONIC ATRIAL FIBRILLATION.

Case reports of ventricular proarrhythmic effects in patients treated with flecainide acetate for atrial fibrillation/flutter have included increased PVCs, VT, ventricular fibrillation (VF), and death.

As with other Class I agents, patients treated with flecainide acetate for atrial flutter have been reported with 1:1 atrioventricular conduction due to slowing the atrial rate.

A paradoxical increase in the ventricular rate also may occur in patients with atrial fibrillation who receive flecainide acetate.

Concomitant negative chronotropic therapy such as digoxin or beta-blockers may lower the risk of this complication.

PROARRHYTHMIC EFFECTS Flecainide acetate, like other antiarrhythmic agents, can cause new or worsened supraventricular or ventricular arrhythmias.

Ventricular proarrhythmic effects range from an increase in frequency of PVCs to the development of more severe ventricular tachycardia, e.g., tachycardia that is more sustained or more resistant to conversion to sinus rhythm, with potentially fatal consequences.

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.

In studies of 225 patients with supraventricular arrhythmia (108 with paroxysmal supraventricular tachycardia and 117 with paroxysmal atrial fibrillation), there were 9 (4%) proarrhythmic events, 8 of them in patients with paroxysmal atrial fibrillation.

Of the 9, 7 (including the one in a PSVT patient) were exacerbations of supraventricular arrhythmias (longer duration, more rapid rate, harder to reverse) while 2 were ventricular arrhythmias, including one fatal case of VT/VF and one wide complex VT (the patient showed inducible VT, however, after withdrawal of flecainide), both in patients with paroxysmal atrial fibrillation and known coronary artery disease.

It is uncertain if flecainide acetate's risk of proarrhythmia is exaggerated in patients with chronic atrial fibrillation (CAF), high ventricular rate, and/or exercise.

Wide complex tachycardia and ventricular fibrillation have been reported in two of 12 CAF patients undergoing maximal exercise tolerance testing.

In patients with complex ventricular arrhythmias, it is often difficult to distinguish a spontaneous variation in the patient's underlying rhythm disorder from drug-induced worsening, so that the following occurrence rates must be considered approximations.

Their frequency appears to be related to dose and to the underlying cardiac disease.

Among patients treated for sustained VT (who frequently also had CHF, a low ejection fraction, a history of myocardial infarction and/or an episode of cardiac arrest), 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.