Flecainide Acetate (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- FLECAINIDE ACETATE
- TAMBOCOR
Boxed Warning
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% (2) 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 bee
Indications and Usage
In patients without structural heart disease, Flecainide Acetate Tablets, USP are indicated for the prevention of: paroxysmal supraventricular tachycardias (PSVT), including atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia and other supraventricular tachycardias of unspecified mechanism associated with disabling symptoms paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms Flecainide Acetate Tablets, USP are also indicated for the prevention of: documented ventricular arrhythmias, such as sustainedventricular tachycardia ( sustained VT), that in the judgment of the physician are life-threatening. Use of Flecainide Acetate Tablets, USP for the treatment of sustainedVT, like other antiarrhythmics, should be initiated in the hospital. The use of Flecainide Acetate Tablets, USP is not recommended in patients with less severe ventricular arrhythmias even if the patients are symptomatic. Because of the proarrhythmic effects of Flecainide Acetate Tablets, USP, its use should be reserved for patients in whom, in the opinion of the physician, the benefits of treatment outweigh the risks. Flecainide Acetate Tablets, USP should not be used in patients with recent myocardial infarction. (See Boxed WARNINGS.) Use of Flecainide Acetate Tablets, USP in chronic atrial fibrillation has not been adequately studied and is not recommended. (See Boxed WARNINGS.) As is the case for other antiarrhythmic agents, there is no evidence from controlled trials that the use of Flecainide Acetate Tablets, USP favorably affects survival or the incidence of sudden death.
Dosage and Administration
For patients with sustainedVT, no matter what their cardiac status, Flecainide Acetate Tablets, USP like other antiarrhythmics, should be initiated in-hospital with rhythm monitoring. Flecainide has a long half-life (12 to 27 hours in patients). Steady-state plasma levels, in patients with normal renal and hepatic function, may not be achieved until the patient has received 3 to 5 days of therapy at a given dose. Therefore, increases in dosage should be made no more frequently than once every four days, since during the first 2 to 3 days of therapy the optimal effect of a given dose may not be achieved. For patients with PSVT and patients with PAF the recommended starting dose is 50 mg every 12 hours. Flecainide Acetate Tablets, USP doses may be increased in increments of 50 mg bid every four days until efficacy is achieved. For PAF patients, a substantial increase in efficacy without a substantial increase in discontinuations for adverse experiences may be achieved by increasing the Flecainide Acetate Tablets, USP dose from 50 mg to 100 mg bid. The maximum recommended dose for patients with paroxysmal supraventricular arrhythmias is 300 mg/day. For sustainedVT the recommended starting dose is 100 mg every 12 hours. This dose may be increased in increments of 50 mg bid every four days until efficacy is achieved. Most patients with sustainedVT do not require more than 150 mg every 12 hours (300 mg/day), and the maximum dose recommended is 400 mg/day. In patients with sustainedVT, use of higher initial doses and more rapid dosage adjustments have resulted in an increased incidence of proarrhythmic events and CHF, particularly during the first few days of dosing (see WARNINGS) . Therefore, a loading dose is not recommended. Intravenous lidocaine has been used occasionally with Flecainide Acetate Tablets, USP while awaiting the therapeutic effect of Flecainide Acetate Tablets, USP. No adverse drug interactions were apparent. However, no formal studies have been performe
Contraindications
Flecainide Acetate Tablets are contraindicated in patients with pre-existing second- or third-degree AV block, or with right bundle branch block when associated with a left hemiblock (bifascicular block), unless a pacemaker is present to sustain the cardiac rhythm should complete heart block occur. Flecainide Acetate Tablets are also contraindicated in the presence of cardiogenic shock or known hypersensitivity to the drug.
Adverse Reactions
In post-myocardial infarction patients with asymptomatic PVCs and non-sustained ventricular tachycardia, flecainide acetate therapy was found to be associated with a 5.1% rate of death and non-fatal cardiac arrest, compared with a 2.3% rate in a matched placebo group. (See WARNINGS.) Adverse effects reported for flecainide acetate, described in detail in the WARNINGSsection, were new or worsened arrhythmias which occurred in 1% of 108 patients with PSVT and in 7% of 117 patients with PAF; and new or exacerbated ventricular arrhythmias which occurred in 7% of 1,330 patients with PVCs, non-sustained or sustainedVT. In patients treated with flecainide acetate for sustained VT, 80% (51/64) of proarrhythmic events occurred within 14 days of the onset of therapy. 198 patients with sustainedVT experienced a 13% incidence of new or exacerbated ventricular arrhythmias when dosage was initiated at 200 mg/day with slow upward titration, and did not exceed 300 mg/day in most patients. In some patients, flecainide acetate treatment has been associated with episodes of unresuscitatable VT or ventricular fibrillation (cardiac arrest). (See WARNINGS.) New or worsened CHF occurred in 6.3% of 1,046 patients with PVCs, non-sustained or sustainedVT. Of 297 patients with sustainedVT, 9.1% experienced new or worsened CHF. New or worsened CHF was reported in 0.4% of 225 patients with supraventricular arrhythmias. There have also been instances of second- (0.5%) or third-degree (0.4%) AV block. Patients have developed sinus bradycardia, sinus pause, or sinus arrest, about 1.2% altogether (see WARNINGS) . The frequency of most of these serious adverse events probably increases with higher trough plasma levels, especially when these trough levels exceed 1 mcg/mL. There have been rare reports of isolated elevations of serum alkaline phosphatase and isolated elevations of serum transaminase levels. These elevations have been asymptomatic and no cause and effect relationship with flecainide ace
Drug Interactions
Flecainide acetate has been administered to patients receiving digitalispreparations or beta-adrenergic blocking agentswithout adverse effects. During administration of multiple oral doses of flecainide acetate to healthy subjects stabilized on a maintenance dose of digoxin, a 13% to 19% increase in plasma digoxinlevels occurred at six hours postdose. In a study involving healthy subjects receiving flecainide acetate and propranololconcurrently, plasma flecainide levels were increased about 20% and propranolollevels were increased about 30% compared to control values. In this formal interaction study, flecainide acetate and propranololwere each found to have negative inotropic effects; when the drugs were administered together, the effects were additive. The effects of concomitant administration of flecainide acetate and propranololon the PR interval were less than additive. In flecainide acetate clinical trials, patients who were receiving beta blockersconcurrently did not experience an increased incidence of side effects. Nevertheless, the possibility of additive negative inotropic effects of beta blockersand flecainide should be recognized. Flecainide is not extensively bound to plasma proteins. In vitrostudies with several drugs which may be administered concomitantly showed that the extent of flecainide binding to human plasma proteins is either unchanged or only slightly less. Consequently, interactions with other drugs which are highly protein bound (e.g., anticoagulants) would not be expected. Flecainide acetate has been used in a large number of patients receiving diureticswithout apparent interaction. Limited data in patients receiving known enzyme inducers ( phenytoin, phenobarbital, carbamazepine) indicate only a 30% increase in the rate of flecainide elimination. In healthy subjects receiving cimetidine(1 gm daily) for one week, plasma flecainide levels increased by about 30% and half-life increased by about 10%. When amiodaroneis added to flecainide ac
Overdosage
No specific antidote has been identified for the treatment of flecainide acetate overdosage. Overdoses ranging up to 8,000 mg have been survived, with peak plasma flecainide concentrations as high as 5.3 mcg/mL. Untoward effects in these cases included nausea and vomiting, convulsions, hypotension, bradycardia, syncope, extreme widening of the QRS complex, widening of the QT interval, widening of the PR interval, ventricular tachycardia, AV nodal block, asystole, bundle branch block, cardiac failure, and cardiac arrest. The spectrum of events observed in fatal cases was much the same as that seen in the non-fatal cases. Death has resulted following ingestion of as little as 1,000 mg; concomitant overdose of other drugs and/or alcohol in many instances undoubtedly contributed to the fatal outcome. Treatment of overdosage should be supportive and may include the following: removal of unabsorbed drug from the gastrointestinal tract, administration of inotropic agents or cardiac stimulants such as dopamine, dobutamine or isoproterenol; mechanically assisted respiration; circulatory assists such as intra-aortic balloon pumping; and transvenous pacing in the event of conduction block. Because of the long plasma half-life of flecainide (12 to 27 hours in patients receiving usual doses), and the possibility of markedly non-linear elimination kinetics at very high doses, these supportive treatments may need to be continued for extended periods of time. Hemodialysis is not an effective means of removing flecainide from the body. Since flecainide elimination is much slower when urine is very alkaline (pH 8 or higher), theoretically, acidification of urine to promote drug excretion may be beneficial in overdose cases with very alkaline urine. There is no evidence that acidification from normal urinary pH increases excretion.