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Flecainide Acetate

Pronunciation

Class: Class Ic Antiarrhythmics
VA Class: CV300
Chemical Name: N-(2-Piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide monoacetate
Molecular Formula: C17H20F6N2O3•C2H4O2
CAS Number: 54143-56-5
Brands: Tambocor

Introduction

Local anesthetic-type class IC antiarrhythmic agent.1 2 3 4 5 6 7 146 147 165 247

Uses for Flecainide Acetate

Ventricular Arrhythmias

Suppression and prevention of recurrent life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia).1 2 3 4 5 24 52 53 77 89 90 91 92 110 125 161 162 165 166 175 176 177 178 179 (See Mortality under Cautions.)

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Supraventricular Tachyarrhythmias

Prevention of paroxysmal supraventricular tachyarrhythmias (PSVT), including AV nodal reentrant tachycardia and AV reentrant tachycardia (Wolff-Parkinson-White syndrome); other symptomatic, including disabling, supraventricular tachycardias of unspecified mechanisms; and symptomatic, disabling supraventricular arrhythmias (paroxysmal atrial fibrillation/flutter [PAF]) in patients without structural heart disease.1 35 110 115 140 192 193 194 197 198 199 200 201 206 218 247

Used in the conversion of recent-onset (≤48 hours duration) atrial fibrillation to normal sinus rhythm.247

Has been used for out-of-hospital self-administration (“pill-in-the-pocket” approach) as a single oral loading dose to terminate recent-onset PAF in carefully selected adults with mild or no heart disease.243 244 224 228 242 May result in reduced hospitalizations and emergency room visits.243 244 224 228 242

Flecainide Acetate Dosage and Administration

General

  • Monitor plasma flecainide concentrations when feasible, especially in patients with severe hepatic1 or renal impairment, severe CHF,1 43 165 or life-threatening ventricular arrhythmias.136 Maintain trough plasma flecainide concentrations at <0.7–1 mcg/mL.1 2 59 70 78 104 165 (See Plasma Concentrations under Pharmacokinetics.)

  • Clinical and ECG monitoring (e.g., Holter monitoring) is recommended during therapy.1 89 165

Administration

Oral Administration

Administer orally in 2 equally divided doses daily at 12-hour intervals.1 2 165

If arrhythmias are not adequately controlled or drug is not well tolerated with twice-daily dosing, may give in 3 divided doses daily at 8-hour intervals.1 2 59 89 146 150 165

Dosage

Available as flecainide acetate; dosage expressed in terms of flecainide.1

Adjust dosage carefully according to individual requirements and response, patient tolerance, and the general condition and cardiovascular status of the patient.1 2 3 89 165

To minimize effects on cardiac conduction, use lowest possible effective dosage.1 2 165

Consider dosage reduction if PR interval increases to ≥300 ms,1 2 165 QRS duration increases to ≥180 ms,1 2 165 QTc interval increases substantially,46 50 89 and/or new bundle-branch block develops.89 1 2 89 165

If 2nd or 3rd degree AV block or bifascicular block occurs, discontinue therapy unless a temporary or implanted artificial ventricular pacemaker is in place to ensure adequate ventricular rate.1 2 89 165

Oral loading doses generally not used since arrhythmogenicity and CHF may occur.1 165 However, single oral loading doses (e.g., 200–300 mg) have been used with apparent safety for conversion of recent-onset atrial fibrillation to normal sinus rhythm in individuals with mild or no structural heart disease.224 228 233 235 236 240 241 242 243 244

Adults

Ventricular Arrhythmias
Oral

Initially, 100 mg every 12 hours.1 2 165 Increase dosage in increments of 50 mg twice daily every 4 days until optimum response is obtained or maximum dosage of 400 mg daily is reached.1 2 165

Dosages >300 mg daily generally not required.1 2 165

Supraventricular Arrhythmias
Oral

Initially, 50 mg every 12 hours.1 192 193 200 Increase dosage in increments of 50 mg twice daily every 4 days until optimum response is obtained or maximum dosage of 300 mg daily is reached.1

Self-administration for Conversion of Paroxysmal Atrial Fibrillation
Oral

Patients ≥70 kg: 300 mg as a single oral loading dose 5 minutes after onset of palpitations.224 242

Patients <70 kg: 200 mg as a single oral loading dose 5 minutes after onset of palpitations.224 242

Remain in sitting or supine position until resolution of palpitations or for ≥4 hours after dose.224 242 Seek medical advice if palpitations do not resolve within 6–8 hours, if previously unexperienced symptoms (e.g., dyspnea, presyncope, syncope) occur, or if marked increase in heart rate occurs.224

Do not take more than one dose during a 24-hour period.224

Prescribing Limits

Adults

Ventricular Arrhythmias
Oral

Maximum 400 mg daily.1 2 165

Supraventricular Arrhythmias
Oral

Maximum 300 mg daily for treatment of PSVT.1

Self-administration for Conversion of Paroxysmal Atrial Fibrillation
Oral

Maximum 300 mg as single oral dose in 24-hour period for adults ≥70 kg.224 242 224

Maximum 200 mg as single oral dose in 24-hour period for adults <70 kg.224 242

Special Populations

Hepatic Impairment

Reduce dosage as necessary.1 3 165 Longer intervals (>4 days) between dosage adjustments are required.1 2 165 Monitor plasma concentrations closely to guide dosage adjustments.1 3 165

Renal Impairment

In patients with Clcr ≤35 mL/minute, initial dosage of 100 mg once daily or 50 mg twice daily is recommended.1 Longer intervals (>4 days) between dosage adjustments are required.1 2 165 Monitor plasma concentrations closely to guide dosage adjustments.1 2 165

Cautions for Flecainide Acetate

Contraindications

  • Preexisting 2nd or 3rd degree AV block, bifascicular block (right bundle branch block associated with left hemiblock),1 2 89 165 or trifascicular block,89 unless pacemaker is in place.

  • Cardiogenic shock.1 2 165

  • Known hypersensitivity to flecainide.1 2 165

Warnings/Precautions

Warnings

Mortality

Excessive rate of mortality or nonfatal cardiac arrest reported in patients with asymptomatic or mildly symptomatic non-life-threatening ventricular arrhythmias and recent MI (>6 days but <2 years previously) (CAST study).161 163 174 175 176 177 181 182 190 191

Limit use of flecainide in patients with ventricular arrhythmias to those with life-threatening arrhythmias;161 163 165 170 176 177 178 181 use in patients with less severe ventricular arrhythmias, even when symptomatic, is not recommended.161 163 165 170 176 177 178

Do not use in patients with recent MI.1

Patients with Chronic Atrial Fibrillation

Not adequately studied in patients with chronic atrial fibrillation; possible VT or VF or paradoxical increase in ventricular rate.1 207 208 209 Use in these patients is not recommended.1 207 208 209

Arrhythmogenic Effects

Potential for new and/or more severe or potentially fatal arrhythmias (principally ventricular tachyarrhythmias but also increased VPCs or supraventricular arrhythmias).1 2 27 43 44 45 46 47 48 49 50 51 52 151 159 165 Risk appears to be related to dosage and underlying cardiac disease.1 2 27 151

Clinical and ECG evaluations are essential prior to and during therapy.1 2 89 Follow recommended dosage schedule closely.1 2 27 165 Monitor plasma drug concentrations and avoid concentrations >1 mcg/mL.27 If possible, avoid concomitant use of other antiarrhythmic agents.27 43 44

Initiation of Therapy

Initiate flecainide therapy in hospital setting with ECG monitoring for patients with sustained VT, regardless or their cardiac status.1 2 89 151 165

Consider initiating flecainide in hospital setting for other patients with underlying structural heart disease1 89 151 165 (particularly those with serious disease)89 136 151 and for patients transferring from therapy with another antiarrhythmic agent in whom discontinuance of the current antiarrhythmic agent is likely to result in life-threatening arrhythmias.1 165

Discontinuance of Therapy

Withdraw flecainide therapy from patients with sustained ventricular arrhythmias in hospital setting under continuous ECG monitoring; 164 172 182 consider hospitalization when withdrawing therapy from patients with nonsustained arrhythmias.172

CHF

Potential for new or worsened CHF, particularly in patients with cardiomyopathy, preexisting severe CHF (NYHA class III or IV), or ejection fraction <30%.1

If CHF or myocardial dysfunction develops, dosage reduction may be necessary.2

Use with caution in patients with a history of CHF or myocardial dysfunction,1 2 89 146 151 154 165 particularly those with advanced failure or dysfunction.1 2 19 27 62 63 89 91 146 Carefully monitor such patients; do not exceed recommended initial dosage.1 2 165 Monitor plasma flecainide concentrations and adjust dosage to maintain trough concentrations <0.7–1 mcg/mL.1 2 165 If progressive CHF occurs despite reduction of flecainide dosage and/or optimum management with other therapy, discontinue flecainide.1 2 154 165

Effects on Cardiac Conduction

To minimize effects on cardiac conduction, use lowest possible effective dosage.1 2 165

Consider dosage reduction if PR interval increases to ≥300 ms,1 2 165 QRS duration increases to ≥180 ms,1 2 165 QTc interval increases substantially,46 50 89 and/or new bundle-branch block develops89 .1 2 89 165

If 2nd or 3rd degree AV block or bifascicular block occurs, discontinue flecainide unless a temporary or implanted artificial ventricular pacemaker is in place to ensure adequate ventricular rate.1 2 89 165

Atypical ventricular tachycardia-like (torsades de pointes-like) arrhythmia reported rarely.1 165

Patients with Sinus Node Dysfunction

Potential for sinus bradycardia, pause, or arrest in patients with sick sinus syndrome (including bradycardia-tachycardia syndrome); use with extreme caution, if at all,136 in such patients.1 2 90 151 165

Initiate therapy in hospital setting for patients with sinus node dysfunction.1 2

Changes in Endocardial Pacing Threshold

Potential for increased endocardial pacing threshold and suppression of ventricular escape rhythms.32 38 39

Use with caution in patients with permanent artificial pacemakers or temporary pacing electrodes;1 2 32 38 39 165 do not administer to patients with existing poor thresholds or nonprogrammable artificial pacemakers unless suitable pacing rescue is available.1 2 165

In patients with pacemakers, determine pacing threshold before and 1 week after initiating therapy and at regular intervals thereafter.1 2 165

Potassium Imbalance

Correct any preexisting potassium imbalance before initiating flecainide.1 165

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk.1 165 Discontinue nursing or the drug.1 165

Pediatric Use

Safety and efficacy not established in children.1 165 Limited data suggest that flecainide may be useful for management of refractory paroxysmal reentrant supraventricular tachycardias in pediatric patients.127

Possible proarrhythmic effects.1 Has been associated with cardiac arrest and sudden death in pediatric patients with structural heart disease.1

Use should be supervised directly by a cardiologist experienced in the treatment of arrhythmias in children.1 Initiate therapy in hospital setting equipped with ECG monitoring.1

Hepatic Impairment

Elimination may be markedly prolonged; use only if benefits clearly outweigh risks.1 165 Monitor plasma concentrations and reduce dosage as necessary.1 3 165

Renal Impairment

Elimination may be impaired; use with caution.1 2 70 165 Monitor plasma concentrations and reduce dosage as necessary.1 165

Common Adverse Effects

Dizziness, visual disturbances,1 2 3 4 5 30 58 59 76 77 78 94 95 96 97 98 101 102 103 104 124 150 165 dyspnea,1 headache,1 2 30 94 95 97 98 102 103 104 165 nausea,1 94 95 97 fatigue,1 2 124 165 palpitation,1 2 165 chest pain.1 2 165

Interactions for Flecainide Acetate

CYP2D6 involved in metabolism.1 245

Antiarrhythmic Agents

Potential for increased risk of arrhythmogenic effects;27 43 91 126 additive, synergistic, or antagonistic cardiac effects; or additive adverse effects.108 112 131 136

Avoid concomitant use with other antiarrhythmic agents if possible;27 43 44 reserve concomitant use for carefully selected and managed patients with severe refractory arrhythmias.77 92 108 110 111 112 122

Diuretics

No apparent interaction when used concomitantly with diuretics in clinical trials.1

Drugs Affecting Hepatic Microsomal Enzymes

CYP2D6 inhibitors: Possible increase in plasma flecainide concentrations, particularly in extensive metabolizers.1 245

CYP2D6 inducers: Potential pharmacokinetic interaction; increased rate of flecainide elimination.1

Protein-bound Drugs

Pharmacokinetic interaction unlikely.1

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Acidifying agents (e.g., ammonium chloride)

Urinary excretion of flecainide increased and elimination half-life decreased in presence of very acidic urine 80 85

Flecainide dosage adjustment may be necessary70

Alkalinizing agents (e.g., high-dose antacids, carbonic anhydrase inhibitors, sodium bicarbonate)

Urinary excretion of flecainide decreased and elimination half-life increased in presence of very alkaline urine 80 85

Flecainide dosage adjustment may be necessary70

Amiodarone

Increased plasma flecainide concentrations1

Reduce flecainide dosage by 30–50%1 131 142 156 157 165 monitor patient closely;1 142 165 monitor plasma flecainide concentrations adjust flecainide dosage as necessary1 142 165

Antacids

No effect on rate or extent of flecainide absorption1 2 70 72

β-adrenergic blocking agents

Potential for additive negative inotropic effects.1 2 165

Increased plasma concentrations of flecainide and propranolol.1 133 165

Carbamazepine

Possible increased rate of flecainide elimination1

Cimetidine

Possible reduction in nonrenal and renal clearance of flecainide135

Possible increased flecainide elimination half-life and increased plasma flecainide concentrations 1

Possible flecainide dosage reduction; further study needed.135

Clozapine

Possible increased plasma flecainide concentrations1 246

Use with caution and monitor closely, especially patients with extensive-metabolizer phenotype1 246

Adjust flecainide and/or clozapine dosage as necessary1 246

Digoxin

Possible increased plasma digoxin concentrations1 132 133 134 165

Monitor for signs of digoxin toxicity133 134

Disopyramide

Potential for negative inotropic effects1

Use concomitantly only if potential benefits outweigh risk1

Milk

Possible reduction of flecainide absorption in infants1

Consider reducing flecainide dosage when milk is removed from infant’s diet1

Phenytoin

Possible increased rate of flecainide elimination1

Phenobarbital

Possible increased rate of flecainide elimination1

Quinidine

Possible increased plasma flecainide concentrations1 245

Use with caution and monitor closely, especially patients with extensive-metabolizer phenotype1 245

Adjust flecainide and/or quinidine dosage as necessary1 245

Verapamil

Potential for negative inotropic effects1

Use concomitantly only if potential benefits outweigh risk1 2 165

Flecainide Acetate Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed following oral administration,1 2 70 71 72 73 165 with peak plasma concentrations generally reached within 2–3 hours.1 2 56 70 71 72 73 165 Absolute bioavailability is approximately 85–90%.2 70

No substantial first-pass metabolism.1 2 70 71 165

Food

Food may slightly decrease rate2 70 but does not affect extent of absorption.1 2 70 72 165

Plasma Concentrations

Trough plasma concentrations are 0.2–1 mcg/mL in most patients successfully treated with flecainide.1 59 77 92 165 189

Increased risk of adverse cardiac effects (e.g., conduction defects, bradycardia) at plasma concentrations >0.7–1 mcg/mL;1 2 70 78 165 possible increased arrhythmogenicity at concentrations >1 mcg/mL.27 45 50 78

Distribution

Extent

Rapidly and apparently widely distributed following IV administration.70 71 79

Appears to be distributed into milk.1 165

Plasma Protein Binding

About 40–50%.1 2 70 81 82 83 165

Elimination

Metabolism

Extensively metabolized, probably in the liver, to 2 major metabolites and at least 3 unidentified minor metabolites;1 70 73 165 unlikely that major metabolites contribute substantially to therapeutic or toxic effects.1 2 70 86

CYP2D6 involved in metabolism.1 245

Elimination Route

Excreted almost completely in urine as unchanged drug and metabolites.1 2 70 73 165

Plasma clearance is decreased when urine pH ≥8.1

Half-life

Biphasic; terminal elimination half-life is about 11.5–16 hours.56 70 72 80

Special Populations

In patients with VPCs,1 2 30 58 59 70 75 76 165 CHF,2 56 70 or renal1 2 70 165 or hepatic1 impairment, plasma clearance is decreased.

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 15–30°C.1 165

Actions

  • Membrane-stabilizing antiarrhythmic agent; exhibits local anesthetic effects.1 2 3 4 5 6 12 13 14 165

  • Principal effect on cardiac tissue appears to be concentration-dependent inhibition of transmembrane influx of extracellular sodium ions via fast sodium channels.6 11 12 13 14 15 16 17

  • Combines with fast sodium channels within the myocardium and inhibits rapid sodium influx, which decreases the maximal rate of depolarization of phase 0 of the action potential.6 11 12 13 14 15 16 17

  • Combines with fast sodium channels in their inactive state12 13 17 and inhibits recovery after repolarization in a time- and voltage-dependent manner, which is associated with subsequent dissociation of the drug from the sodium channels.12 13 17

  • Exhibits electrophysiologic effects characteristic of class IC antiarrhythmic agents, which slowly attach to and dissociate from transmembrane sodium channels.1 2 3 4 5 12 13 14 20 165

  • Produces dose-related decrease in intracardiac conduction throughout the heart, with the most marked effect on conduction within the His-Purkinje system.1 2 3 4 5 22 24 165

  • Produces dose-related increases in PR, QRS, AH, and, to a lesser degree, QT intervals.1 2 3 22 23 24 25 27 30 52 53 58 59 76 89 94 102 104 165

  • May increase atrial effective refractory period (ERP) 22 23 24 26 31 36 77 145 and ventricular ERP.23 24 25 36 52 53 77 92

  • Exhibits a mild to moderate negative inotropic effect.1 2 10 18 19 60 61 62 63 64 65 66 67 68 165

Advice to Patients

  • Importance of not altering therapy without first consulting clinician.162 164 172

  • Advise patients who self-administer loading dose for conversion of paroxysmal atrial fibrillation to remain in a supine or sitting position until resolution of palpitations or for a period of at least 4 hours following the dose.224 242 Importance of informing clinician if palpitations do not resolve within 6–8 hours, previously unexperienced symptoms (e.g., dyspnea, presyncope, syncope) occur, or a marked increase in heart rate develops.224

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Flecainide Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

50 mg*

Flecainide Acetate Tablets

Tambocor

3M

100 mg*

Flecainide Acetate Tablets

Tambocor (scored)

3M

150 mg*

Flecainide Acetate Tablets

Tambocor (scored)

3M

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Flecainide Acetate 100MG Tablets (ROXANE): 60/$83.97 or 180/$232.94

Flecainide Acetate 150MG Tablets (ROXANE): 60/$119.00 or 180/$331.96

Flecainide Acetate 50MG Tablets (ROXANE): 60/$58.99 or 180/$158.98

Tambocor 100MG Tablets (GRACEWAY PHARMACEUTICALS): 60/$229.98 or 180/$659.99

Tambocor 150MG Tablets (GRACEWAY PHARMACEUTICALS): 60/$310.00 or 180/$886.02

Tambocor 50MG Tablets (GRACEWAY PHARMACEUTICALS): 60/$145.97 or 180/$421.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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