Flecainide

Flecainide
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi

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Black Box Warning

See full prescribing information for complete Boxed Warning. Mortality: Flecainide 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 compared with that seen in patients assigned to a carefully matched placebo-treated group. This rate was 16/315 (5.1%) for flecainide and 7/309 (2.3%) for the matched placebo. The average duration of treatment with flecainide 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), 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 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 for atrial fibrillation/flutter have included increased PVCs, VT, ventricular fibrillation (VF), and death. As with other Class I agents, patients treated with flecainide 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. Concomitant negative chronotropic therapy such as digoxin or beta-blockers may lower the risk of this complication.

Overview

Flecainide is an antiarrhythmic that is FDA approved for the {{{indicationType}}} of paroxysmal supraventricular tachycardias (PSVT), paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms, sustained ventricular tachycardia (sustained VT). Fecainide is also indicated for the treatment of documented ventricular arrhythmias, such as sustained VT. There is a Black Box Warning for this drug as shown here. Common adverse reactions include palpitations, nausea, dizziness, headache, blurred vision, photopsia, dyspnea, and fatigue.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Condition1

• Dosing Information

• Dosage

Condition2

• Dosing Information

• Dosage

Condition3

• Dosing Information

• Dosage

Condition4

• Dosing Information

• Dosage

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Flecainide in adult patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Flecainide in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding FDA-Labeled Use of Flecainide in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Flecainide in pediatric patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Flecainide in pediatric patients.

Contraindications

• Condition1

Warnings

See full prescribing information for complete Boxed Warning. Mortality: Flecainide 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 compared with that seen in patients assigned to a carefully matched placebo-treated group. This rate was 16/315 (5.1%) for flecainide and 7/309 (2.3%) for the matched placebo. The average duration of treatment with flecainide 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), 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 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 for atrial fibrillation/flutter have included increased PVCs, VT, ventricular fibrillation (VF), and death. As with other Class I agents, patients treated with flecainide 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. Concomitant negative chronotropic therapy such as digoxin or beta-blockers may lower the risk of this complication.

• Description

Precautions

• Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Flecainide in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Flecainide in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Flecainide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Flecainide during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Flecainide with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Flecainide with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Flecainide with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Flecainide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Flecainide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Flecainide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Flecainide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Flecainide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Flecainide in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Flecainide in the drug label.

Condition1

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Flecainide in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Flecainide in the drug label.

Pharmacology

There is limited information regarding Flecainide Pharmacology in the drug label.

Mechanism of Action

• Flecainide has local anesthetic activity and belongs to the membrane stabilizing (Class 1) group of antiarrhythmic agents; it has electrophysiologic effects characteristic of the IC class of antiarrhythmics.

Electrophysiology

• In man, flecainide produces a dose-related decrease in intracardiac conduction in all parts of the heart with the greatest effect on the His-Purkinje system (H-V conduction). Effects upon atrioventricular (AV) nodal conduction time and intra-atrial conduction times, although present, are less pronounced than those on ventricular conduction velocity. Significant effects on refractory periods were observed only in the ventricle. Sinus node recovery times (corrected) following pacing and spontaneous cycle lengths are somewhat increased. This latter effect may become significant in patients with sinus node dysfunction.

• Flecainide causes a dose-related and plasma-level related decrease in single and multiple PVCs and can suppress recurrence of ventricular tachycardia. In limited studies of patients with a history of ventricular tachycardia, flecainide has been successful 30 to 40% of the time in fully suppressing the inducibility of arrhythmias by programmed electrical stimulation. Based on PVC suppression, it appears that plasma levels of 0.2 to 1 mcg/mL may be needed to obtain the maximal therapeutic effect. It is more difficult to assess the dose needed to suppress serious arrhythmias, but trough plasma levels in patients successfully treated for recurrent ventricular tachycardia were between 0.2 and 1 mcg/mL. Plasma levels above 0.7 to 1 mcg/mL are associated with a higher rate of cardiac adverse experiences such as conduction defects or bradycardia. The relation of plasma levels to proarrhythmic events is not established, but dose reduction in clinical trials of patients with ventricular tachycardia appears to have led to a reduced frequency and severity of such events.

Hemodynamics

• Flecainide does not usually alter heart rate, although bradycardia and tachycardia have been reported occasionally.

• In animals and isolated myocardium, a negative inotropic effect of flecainide has been demonstrated. Decreases in ejection fraction, consistent with a negative inotropic effect, have been observed after single administration of 200 to 250 mg of the drug in man; both increases and decreases in ejection fraction have been encountered during multidose therapy in patients at usual therapeutic doses.

Structure

• Flecainide acetate, USP is an antiarrhythmic drug available in tablets and is benzamide, N-(2-piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)-monoacetate. The structural formula is as follows:

This image is provided by the National Library of Medicine.

• Flecainide acetate, USP is a white crystalline substance with a pKa of 9.3. It has an aqueous solubility of 48.4 mg/mL at 37°C.

• Each tablet, for oral administration, contains 50 mg, 100 mg or 150 mg of flecainide acetate, USP. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline celulose, pregelatinized starch and sodium stearyl fumarate.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Flecainide in the drug label.

Pharmacokinetics

• Following oral administration, the absorption of flecainide is nearly complete. Peak plasma levels are attained at about three hours in most individuals (range, 1 to 6 hours). Flecainide does not undergo any consequential presystemic biotransformation (first-pass effect). Food or antacid do not affect absorption. Milk, however, may inhibit absorption in infants. A reduction in flecainide dosage should be considered when milk is removed from the diet of infants.

• The apparent plasma half-life averages about 20 hours and is quite variable (range, 12 to 27 hours) after multiple oral doses in patients with premature ventricular contractions (PVCs). With multiple dosing, plasma levels increase because of its long half-life with steady-state levels approached in 3 to 5 days; once at steady-state, no additional (or unexpected) accumulation of drug in plasma occurs during chronic therapy. Over the usual therapeutic range, data suggest that plasma levels in an individual are approximately proportional to dose, deviating upwards from linearity only slightly (about 10 to 15% per 100 mg on average).

• In healthy subjects, about 30% of a single oral dose (range, 10 to 50%) is excreted in urine as unchanged drug. The two major urinary metabolites are meta-O-dealkylated flecainide (active, but about one-fifth as potent) and the meta-O-dealkylated lactam of flecainide (non-active metabolite). These two metabolites (primarily conjugated) account for most of the remaining portion of the dose. Several minor metabolites (3% of the dose or less) are also found in urine; only 5% of an oral dose is excreted in feces. In patients, free (unconjugated) plasma levels of the two major metabolites are very low (less than 0.05 mcg/mL).

• In vitro metabolic studies have confirmed that cytochrome P450IID6 is involved in the metabolism of flecainide.

• When urinary pH is very alkaline (8 or higher), as may occur in rare conditions (e.g., renal tubular acidosis, strict vegetarian diet), flecainide elimination from plasma is much slower.

• The elimination of flecainide from the body depends on renal function (i.e., 10 to 50% appears in urine as unchanged drug). With increasing renal impairment, the extent of unchanged drug excretion in urine is reduced and the plasma half-life of flecainide is prolonged. Since flecainide is also extensively metabolized, there is no simple relationship between creatinine clearance and the rate of flecanide elimination from plasma.

• In patients with NYHA class III congestive heart failure (CHF), the rate of flecainide elimination from plasma (mean half-life, 19 hours) is moderately slower than for healthy subjects (mean half-life, 14 hours), but similar to the rate for patients with PVCs without CHF. The extent of excre- tion of unchanged drug in urine is also similar.

• Under one year of age, currently available data are limited but suggest that the half-life at birth may be as long as 29 hours, decreasing to 11to 12 hours by three months of age and 6 hours by one year of age. The pharmacokinetics in hydropic infants have not been studied, but case reports suggest prolonged elimination. In children aged 1 year to 12 years the half-life is approximately 8 hours. In adolescents (age 12 to 15) the plasma elimination half-life is approximately 11 to 12 hours. Since milk may inhibit absorption in infants, a reduction in flecainide dosage should be considered when milk is removed from the diet (e.g., gastroenteritis, weaning). Plasma trough flecainide levels should be monitored during major changes in dietary milk intake.

• From age 20 to 80, plasma levels are only slightly higher with advancing age; flecainide elimination from plasma is somewhat slower in elderly subjects than in younger subjects. Patients up to age 80+ have been safely treated with usual dosages.

• The extent of flecainide binding to human plasma proteins is about 40% and is independent of plasma drug level over the range of 0.015 to about 3.4 mcg/mL. Thus, clinically significant drug interactions based on protein binding effects would not be expected.

• Hemodialysis removes only about 1% of an oral dose as unchanged flecainide.

• Small increases in plasma digoxin levels are seen during coadministration of flecainide with digoxin. Small increases in both flecainide and propranolol plasma levels are seen during coadministration of these two drugs.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Flecainide in the drug label.

Clinical Studies

• In two randomized, crossover, placebo-controlled clinical trials of 16 weeks double-blind duration, 79% of patients with paroxysmal supraventricular tachycardia (PSVT) receiving flecainide were attack free, whereas 15% of patients receiving placebo remained attack free. The median time-before-recurrence of PSVT in patients receiving placebo was 11 to 12 days, whereas over 85% of patients receiving flecainide had no recurrence at 60 days.

• In two randomized, crossover, placebo-controlled clinical trials of 16 weeks double-blind duration, 31% of patients with paroxysmal atrial fibrillation/flutter (PAF) receiving flecainide were attack free, whereas 8% receiving placebo remained attack free. The median time-before-recurrence of PAF in patients receiving placebo was about 2 to 3 days, whereas for those receiving flecainide the median time-before-recurrence was 15 days.

How Supplied

• Flecainide Acetate Tablets USP are available as:

• 50 mg: White to off-white, round, flat-faced, beveled-edge, unscored tablet. Debossed with stylized b on one side and 859 on the other side. They are available in bottles of 100 tablets.

• 100 mg: White to off-white, oval, flat-faced, beveled-edge, scored tablet. Debossed with stylized b on one side and 860/100 on the scored side. They are available in bottles of 100 tablets.

• 150 mg: White to off-white, oval, flat-faced, beveled-edge, scored tablet. Debossed with stylized b on one side and 861/150 on the scored side. They are available in bottles of 100 tablets.

• Store at 20º to 25°C (68° to 77°F)

• Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

• KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

Storage

There is limited information regarding Flecainide Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Flecainide in the drug label.

Precautions with Alcohol

• Alcohol-Flecainide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• Tambocor®

Look-Alike Drug Names

• Tambocor® — Pamelor®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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