Tambocor

Generic Name: Flecainide Acetate
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

Introduction

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

Uses for Tambocor

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.)

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}

Tambocor 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} QT_c 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 Cl_cr ≤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 Tambocor

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 disease^{1 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} QT_c 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 Tambocor

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

Tambocor 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 rate^{2 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 renal^{1 2 70 165} or hepatic¹ impairment, plasma clearance is decreased.

Stability

Storage

Oral

Tablets

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

ActionsActions

• 
  

  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 state^{12 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 03/2011. 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 (MYLAN): 60/$83.98 or 180/$232.95

Flecainide Acetate 150MG Tablets (MYLAN): 60/$114.98 or 180/$319.93

Flecainide Acetate 50MG Tablets (ROXANE): 60/$57.99 or 180/$155.97

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

Tambocor 150MG Tablets (GRACEWAY PHARMACEUTICALS): 60/$310 or 180/$886.02

Tambocor 50MG Tablets (GRACEWAY PHARMACEUTICALS): 60/$145.98 or 180/$421.98

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, in