flecainide acetate
Tambocor

Available forms
Available by prescription only
Tablets: 50 mg, 100 mg, 150 mg

Indications and dosages
 Sustained ventricular tachycardia. Adults: 100 mg P.O. q 12 hours. May increase in increments of 50 mg b.i.d. q 4 days until efficacy is achieved. Maximum dose is 400 mg daily.
 Paroxysmal supraventricular tachycardia, paroxysmal atrial fibrillation or flutter in patients without structural heart disease. Adults: 50 mg P.O. q 12 hours. May increase in increments of 50 mg b.i.d. q 4 days until efficacy is achieved. Maximum dose is 300 mg daily.
≡ Dosage adjustment. Reduce dosage in patients with renal impairment (creatinine clearance of less than 35 ml/minute) beginning at 100 mg/day (50 mg b.i.d.); increase dosage cautiously at intervals longer than 4 days. For patients with less severe renal impairment, initial dose is 100 mg q 12 hours, increasing cautiously at intervals longer than 4 days.

Pharmacodynamics
Antiarrhythmic action: A class IC antiarrhythmic, flecainide suppresses SA node automaticity and prolongs conduction in the atria, AV node, ventricles, accessory pathways, and His-Purkinje system. It has the most pronounced effect on the His-Purkinje system, as shown by QRS-complex widening; this leads to a prolonged QT interval. The drug has relatively little effect on action potential duration except in Purkinje’s fibers, where it shortens it. A proarrhythmic (arrhythmogenic) effect may result from the potent effects of the drug on the conduction system. Effects on the sinus node are strongest in patients with sinus node disease (sick sinus syndrome). Flecainide also exerts a moderate negative inotropic effect.

Pharmacokinetics
Absorption: Rapidly and almost completely absorbed from the GI tract; bioavailability of commercially available tablets is 85% to 90%.
Distribution: Apparently well distributed throughout the body. Only about 40% binds to plasma proteins. Trough serum levels ranging from 0.2 to 1 mcg/ml provide the greatest therapeutic benefit. Trough serum levels higher than 0.7 to 1 mcg/ml have been associated with increased adverse effects.
Metabolism: Metabolized in the liver to inactive metabolites. About 30% of an orally administered dose escapes metabolism and is excreted in the urine unchanged.
Excretion: Elimination half-life averages about 20 hours. Plasma half-life may be prolonged in patients with heart failure and renal disease.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with cardiogenic shock, second- or third-degree AV block, or right bundle branch block with a left hemiblock (in the absence of an artificial pacemaker). Drug has proarrhythmic effects in patients with atrial fibrillation or flutter; therefore it isn’t recommended for these patients.
  Use cautiously in patients with heart failure, cardiomyopathy, severe renal or hepatic disease, prolonged QT interval, sick sinus syndrome, or blood dyscrasia.

Interactions
Drug-drug. Acidifying and alkalizing agents: Alkalization decreases renal flecainide excretion; acidification increases it. Monitor patient carefully.
Amiodarone, quinidine: May increase plasma flecainide levels. Monitor drug levels and patient for toxicity; dosage adjustment may be needed.
Beta blockers: May cause additive negative inotropic effects. Monitor patient carefully.
Carbonic anhydrase inhibitors, high-dose antacids, sodium bicarbonate: Markedly affects urine acidity. Monitor patient for subtherapeutic or toxic levels and effects.
Cimetidine: May decrease renal and nonrenal flecainide clearance. Monitor patient carefully.
Digoxin: Increases serum digoxin levels. Monitor digoxin levels.
Disopyramide, verapamil: Causes negative inotropic effects. Don’t give these drugs with flecainide unless risks outweigh benefits.
Drug-lifestyle. Smoking: May lower serum flecainide levels. Discourage smoking.

Adverse reactions
CNS: dizziness, headache, fatigue, tremor, anxiety, insomnia, depression, malaise, paresthesia, ataxia, vertigo, light-headedness, syncope, asthenia, fever.
CV: new or worsened arrhythmias, chest pain, flushing, edema, heart failure, cardiac arrest, palpitations.
EENT: blurred vision and other visual disturbances.
GI: nausea, constipation, abdominal pain, dyspepsia, vomiting, diarrhea, anorexia.
Respiratory: dyspnea.
Skin: rash.

Effects on lab test results
None reported.

Overdose and treatment
Effects of overdose include increased PR and QT intervals, increased QRS complex duration, decreased myocardial contractility, conduction disturbances, and hypotension.
 Treatment usually involves symptomatic and supportive measures along with ECG, blood pressure, and respiratory monitoring. Inotropic agents, including dopamine and dobutamine, may be used. Hemodynamic support, including use of an intra-aortic balloon pump and transvenous pacing, may be needed. Because of long half-life of drug, supportive measures may need to be continued for extended periods. Hemodialysis is ineffective in reducing serum drug levels.

Special considerations
 ALERT Drug has been linked to excessive mortality or nonfatal cardiac arrest rate. Restrict use to those patients for whom benefits outweigh risks.
• Tambocor is a strong negative inotrope and may cause or worsen heart failure, especially in those with cardiomyopathy, heart failure, or low ejection fraction.
• Hypokalemia or hyperkalemia may alter drug effects and should be corrected before giving drug.
• Therapy should begin in the hospital with careful monitoring of patient with symptomatic heart failure, sinus node dysfunction, sustained ventricular tachycardia, or underlying structural heart disease and in patient changing from another antiarrhythmic in whom discontinuation of current antiarrhythmic is likely to cause life-threatening arrhythmias.
• Loading doses may worsen arrhythmias and therefore aren’t recommended. Adjust dosage at intervals of at least 4 days because of long half-life.
• Most patients can be maintained on a q-12-hour dosage schedule, but some need drug every 8 hours.
• Twice-daily dosing improves patient compliance.
• Full therapeutic effect of drug may take 3 to 5 days.
• Flecainide is a class IC antiarrhythmic. Adverse effects increase when trough serum levels exceed 0.7 mcg/ml. Periodically monitor blood levels, especially in patients with renal failure or heart failure. Therapeutic levels range from 0.2 to 1 mcg/ml.
• Drug may increase acute and chronic endocardial pacing thresholds and may suppress ventricular escape rhythms. Determine pacing threshold before giving drug, after 1 week of therapy, and regularly thereafter. Don’t give to patients with poor thresholds or nonprogrammable artificial pacemakers unless pacing rescue is available.
• In heart failure and myocardial dysfunction, initial dose shouldn’t exceed 100 mg every 12 hours; common initial dose is 50 mg every 12 hours.
• Use in hepatic impairment hasn’t been fully evaluated; however, because flecainide is metabolized extensively (probably in the liver), use in patients with significant hepatic impairment only when benefits clearly outweigh risks. Dosage reduction may be needed; monitor patient carefully for signs of toxicity. Monitor serum levels.
Breast-feeding patients
• Limited data indicate that drug appears in breast milk. Breast-feeding isn’t recommended during flecainide therapy because of the risk of adverse effects in infant.
Pediatric patients
• Safety and efficacy haven’t been established in children younger than age 18. Limited data suggest drug is useful in management of paroxysmal reentrant supraventricular tachycardia.
Geriatric patients
• Elderly patients are more susceptible to adverse effects. Monitor these patients carefully.

Patient education
• Advise patient to closely follow administration instruction.
• Warn patient of potential adverse drug effects.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use