FDA

Flecainide Acetate

Approved 14 Jan 2003OralTablet

The FDA lists this product in 30 strengths and forms.

Indications

In patients without structural heart disease, flecainide acetate is 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 is also indicated for the prevention of:
documented ventricular arrhythmias, such as sustained ventricular tachycardia ( sustained VT), that in the judgment of the physician are life-threatening. Use of flecainide acetate for the treatment of sustained VT, like other antiarrhythmics, should be initiated in the hospital. The use of flecainide acetate 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, its use should be reserved for patients in whom, in the opinion of the physician, the benefits of treatment outweigh the risks. Flecainide acetate should not be used in patients with recent myocardial infarction. (See Boxed WARNINGS .) Use of flecainide acetate 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 favorably affects survival or the incidence of sudden death.

Contraindications

Flecainide acetate is 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 is also contraindicated in the presence of cardiogenic shock or known hypersensitivity to the drug.

Warnings and precautions

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.

At a glance

Brand name: Flecainide Acetate
Route: Oral
Dosage form: Tablet
Applicant: Hikma
Status: Prescription
FDA approval: 14 Jan 2003
Application: ANDA076278-003

Indications

In patients without structural heart disease, flecainide acetate is 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 is also indicated for the prevention of:
documented ventricular arrhythmias, such as sustained ventricular tachycardia ( sustained VT), that in the judgment of the physician are life-threatening. Use of flecainide acetate for the treatment of sustained VT, like other antiarrhythmics, should be initiated in the hospital. The use of flecainide acetate 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, its use should be reserved for patients in whom, in the opinion of the physician, the benefits of treatment outweigh the risks. Flecainide acetate should not be used in patients with recent myocardial infarction. (See Boxed WARNINGS .) Use of flecainide acetate 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 favorably affects survival or the incidence of sudden death.

Contraindications

Warnings and precautions

Interactions

Drug Interactions Flecainide has been administered to patients receiving digitalis preparations or beta-adrenergic blocking agents without adverse effects. During administration of multiple oral doses of flecainide to healthy subjects stabilized on a maintenance dose of digoxin , a 13% to 19% increase in plasma digoxin levels occurred at six hours postdose. In a study involving healthy subjects receiving flecainide and propranolol concurrently, plasma flecainide levels were increased about 20% and propranolol levels were increased about 30% compared to control values.

In this formal interaction study, flecainide and propranolol were each found to have negative inotropic effects; when the drugs were administered together, the effects were additive. The effects of concomitant administration of flecainide and propranolol on the PR interval were less than additive. In flecainide clinical trials, patients who were receiving beta blockers concurrently did not experience an increased incidence of side effects.

Nevertheless, the possibility of additive negative inotropic effects of beta blockers and flecainide should be recognized. Flecainide is not extensively bound to plasma proteins. In vitro studies 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 has been used in a large number of patients receiving diuretics without 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 amiodarone is added to flecainide therapy, plasma flecainide levels may increase two-fold or more in some patients, if flecainide dosage is not reduced. (See DOSAGE AND ADMINISTRATION ) Drugs that inhibit cytochrome P450IID6, such as quinidine , might increase the plasma concentrations of flecainide in patients that are on chronic flecainide therapy; especially if these patients are extensive metabolizers. There has been little experience with the coadministration of flecainide and either disopyramide or verapamil .

Because both of these drugs have negative inotropic properties and the effects of coadministration with flecainide are unknown, neither disopyramide nor verapamil should be administered concurrently with flecainide unless, in the judgment of the physician, the benefits of this combination outweigh the risks. There has been too little experience with the coadministration of flecainide with nifedipine or diltiazem to recommend concomitant use.

Adverse reactions

In post-myocardial infarction patients with asymptomatic PVCs and non-sustained ventricular tachycardia, flecainide 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, described in detail in the WARNINGS section, 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 1330 patients with PVCs, non-sustained or sustained VT.

In patients treated with flecainide for sustained VT, 80% (51/64) of proarrhythmic events occurred within 14 days of the onset of therapy. 198 patients with sustained VT 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 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 1046 patients with PVCs, non-sustained or sustained VT. Of 297 patients with sustained VT, 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 has been established. In foreign postmarketing surveillance studies, there have been rare reports of hepatic dysfunction including reports of cholestasis and hepatic failure, and extremely rare reports of blood dyscrasias.

Although no cause and effect relationship has been established, it is advisable to discontinue flecainide in patients who develop unexplained jaundice or signs of hepatic dysfunction or blood dyscrasias in order to eliminate flecainide as the possible causative agent. Incidence figures for other adverse effects in patients with ventricular arrhythmias are based on a multicenter efficacy study, utilizing starting doses of 200 mg/day with gradual upward titration to 400 mg/day.

Patients were treated for an average of 4.7 months, with some receiving up to 22 months of therapy. In this trial, 5.4% of patients discontinued due to non-cardiac adverse effects. Table 1: Most Common Non-Cardiac Effects in Ventricular Arrhythmia Patients Treated with Flecainide in the Multicenter Study Adverse Effect Incidence All 429 Patients at Any Dose Incidence by Dose During Upward Titration 200 mg/Day (N=426) 300 mg/Day (N=293) 400 mg/Day (N=100) Dizziness Dizziness includes reports of dizziness, lightheadedness, faintness, unsteadiness, near syncope, etc. 18.9% 11.0% 10.6% 13.0% Visual Disturbances Visual disturbance includes reports of blurred vision, difficulty in focusing, spots before eyes, etc. 15.9% 5.4% 12.3% 18.0% Dyspnea 10.3% 5.2% 7.5% 4.0% Headache 9.6% 4.5% 6.1% 9.0% Nausea 8.9% 4.9% 4.8% 6.0% Fatigue 7.7% 4.5% 4.4% 3.0% Palpitation 6.1% 3.5% 2.4% 7.0% Chest Pain 5.4% 3.1% 3.8% 1.0% Asthenia 4.9% 2.6% 2.0% 4.0% Tremor 4.7% 2.4% 3.4% 2.0% Constipation 4.4% 2.8% 2.1% 1.0% Edema 3.5% 1.9% 1.4% 2.0% Abdominal Pain 3.3% 1.9% 2.4% 1.0% The following additional adverse experiences, possibly related to flecainide therapy and occurring in 1% to less than 3% of patients, have been reported in acute and chronic studies: Body as a Whole: malaise, fever; Cardiovascular: tachycardia, sinus pause or arrest; Gastrointestinal: vomiting, diarrhea, dyspepsia, anorexia; Skin: rash; Visual: diplopia; Nervous System: hypoesthesia, paresthesia, paresis, ataxia, flushing, increased sweating, vertigo, syncope, somnolence, tinnitus; Psychiatric: anxiety, insomnia, depression.

The following additional adverse experiences, possibly related to flecainide, have been reported in less than 1% of patients: Body as a Whole: swollen lips, tongue and mouth; arthralgia, bronchospasm, myalgia; Cardiovascular: angina pectoris, second-degree and third-degree AV block, bradycardia, hypertension, hypotension; Gastrointestinal: flatulence; Urinary System: polyuria, urinary retention; Hematologic: leukopenia, granulocytopenia, thrombocytopenia; Skin: urticaria, exfoliative dermatitis, pruritus, alopecia; Visual: eye pain or irritation, photophobia, nystagmus; Nervous System: twitching, weakness, change in taste, dry mouth, convulsions, impotence, speech disorder, stupor, neuropathy; Respiratory: pneumonitis/pulmonary infiltration possibly due to chronic flecainide treatment; Psychiatric: amnesia, confusion, decreased libido, depersonalization, euphoria, morbid dreams, apathy.

For patients with supraventricular arrhythmias, the most commonly reported noncardiac adverse experiences remain consistent with those known for patients treated with flecainide for ventricular arrhythmias. Dizziness is possibly more frequent in PAF patients.

Flecainide Acetate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Flecainide Acetate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information