No

Antiarrhythmic Agent, Class I-C

Prevention and suppression of documented life-threatening ventricular arrhythmias (eg, sustained ventricular tachycardia); controlling symptomatic, disabling supraventricular tachycardias in patients without structural heart disease in whom other agents fail

C

Hypersensitivity to flecainide or any component; pre-existing second- or third-degree AV block or with right bundle branch block when associated with a left hemiblock (bifascicular block) (except in patients with a functioning artificial pacemaker); cardiogenic shock; coronary artery disease (based on CAST study results); concurrent use of ritonavir or amprenavir

Not recommend for patients with chronic atrial fibrillation. A worsening or new arrhythmia may occur (proarrhythmic effect). Use caution in heart failure (may precipitate or exacerbate CHF). Dose-related increases in PR, QRS, and QT intervals occur. Use with caution in sick sinus syndrome or with permanent pacemakers or temporary pacing wires (can increase endocardial pacing thresholds). Pre-existing hypokalemia or hyperkalemia should be corrected before initiation (can alter drug's effect). Cautious use in significant hepatic impairment.

>10%:

Central nervous system: Dizziness (19% to 30%)

Ocular: Visual disturbances (16%)

Respiratory: Dyspnea (~10%)

1% to 10%:

Cardiovascular: Palpitations (6%), chest pain (5%), edema (3.5%), tachycardia (1% to 3%), proarrhythmic (4% to 12%), sinus node dysfunction (1.2%)

Central nervous system: Headache (4% to 10%), fatigue (8%), nervousness (5%) additional symptoms occurring at a frequency between 1% and 3%: fever, malaise, hypoesthesia, paresis, ataxia, vertigo, syncope, somnolence, tinnitus, anxiety, insomnia, depression

Dermatologic: Rash (1% to 3%)

Gastrointestinal: Nausea (9%), constipation (1%), abdominal pain (3%), anorexia (1% to 3%), diarrhea (0.7% to 3%)

Neuromuscular & skeletal: Tremor (5%), weakness (5%), paresthesias (1%)

Ocular: Diplopia (1% to 3%), blurred vision

<1% (Limited to important or life-threatening symptoms): Bradycardia, paradoxical increase in ventricular rate in atrial fibrillation/flutter, heart block, increased P-R, QRS duration, ventricular arrhythmias, congestive heart failure, flushing, A-V block, angina, hypertension, hypotension, amnesia, confusion, decreased libido, depersonalization, euphoria, apathy, nervousness, twitching, neuropathy, weakness, taste disturbance, urticaria, exfoliative dermatitis, pruritus, alopecia, flatulence, xerostomia, blood dyscrasias, possible hepatic dysfunction, paresthesia, eye pain, photophobia, bronchospasm, pneumonitis, swollen lips/tongue/mouth, arthralgia, myalgia, polyuria, urinary retention, leukopenia, granulocytopenia, thrombocytopenia, metallic taste, alters pacing threshold

Case reports: Tardive dyskinesia, corneal deposits

Has a narrow therapeutic index and severe toxicity may occur slightly above the therapeutic range, especially if combined with other antiarrhythmic drugs. (Acute single ingestion of twice the daily therapeutic dose is life-threatening.) Symptoms of overdose include increases in P-R, QRS, Q-T intervals and amplitude of the T wave, A-V block, bradycardia, hypotension, ventricular arrhythmias (monomorphic or polymorphic ventricular tachycardia), and asystole; other symptoms include dizziness, blurred vision, headache, and GI upset.

Treatment is supportive, using conventional treatment (fluids, positioning, anticonvulsants, antiarrhythmics). Note: Type Ia antiarrhythmic agents should not be used to treat cardiotoxicity caused by type Ic drugs; sodium bicarbonate may reverse QRS prolongation, bradycardia and hypotension; ventricular pacing may be needed; hemodialysis only of possible benefit for tocainide or flecainide overdose in patients with renal failure.

CYP2D6 enzyme substrate

Quinidine may decrease flecainide's metabolism; monitor cardiac status.

Digoxin's serum concentration may increase slightly.

Amiodarone increases in flecainide plasma levels; consider reducing flecainide dose by 25% to 33% with concurrent use.

Amprenavir and ritonavir may increase cardiotoxicity of flecainide (decrease metabolism).

Propranolol (and possibly other beta-blockers) increases flecainide blood levels, and propranolol blood levels are increased with concurrent use; monitor for excessive negative inotropic effects.

Urinary alkalinizers (antacids, sodium bicarbonate, acetazolamide) may increase flecainide blood levels.

Class Ic antiarrhythmic; slows conduction in cardiac tissue by altering transport of ions across cell membranes; causes slight prolongation of refractory periods; decreases the rate of rise of the action potential without affecting its duration; increases electrical stimulation threshold of ventricle, HIS-Purkinje system; possesses local anesthetic and moderate negative inotropic effects

Absorption: Oral: Rapid

Distribution: Adults: V_d: 5-13.4 L/kg

Protein binding: 40% to 50% (alpha₁ glycoprotein)

Bioavailability: 85% to 90%

Metabolism: In the liver

Half-life: Infants: 11-12 hours; Children: 8 hours; Adults: 7-22 hours, increased with congestive heart failure or renal dysfunction; End-stage renal disease: 19-26 hours

Time to peak serum concentration: Within 1.5-3 hours

Elimination: 80% to 90% excreted in urine as unchanged drug and metabolites (10% to 50%)

Oral:

Initial: 3 mg/kg/day or 50-100 mg/m²/day in 3 divided doses

Usual: 3-6 mg/kg/day or 100-150 mg/m²/day in 3 divided doses; up to 11 mg/kg/day or 200 mg/m²/day for uncontrolled patients with subtherapeutic levels

Adults:

Life-threatening ventricular arrhythmias:

Initial: 100 mg every 12 hours

Increase by 50-100 mg/day (given in 2 doses/day) every 4 days; maximum: 400 mg/day.

Use of higher initial doses and more rapid dosage adjustments have resulted in an increased incidence of proarrhythmic events and congestive heart failure, particularly during the first few days. Do not use a loading dose. Use very cautiously in patients with history of congestive heart failure or myocardial infarction.

Prevention of paroxysmal supraventricular arrhythmias in patients with disabling symptoms but no structural heart disease:

Initial: 50 mg every 12 hours

Increase by 50 mg twice daily at 4-day intervals; maximum: 300 mg/day.

Dosing adjustment in severe renal impairment: Cl_cr <35 mL/minute: Decrease initial dose to 50 mg every 12 hours; increase doses at intervals >4 days monitoring EKG levels closely.

Dialysis: Not dialyzable (0% to 5%) via hemo- or peritoneal dialysis; no supplemental dose necessary.

Dosing adjustment/comments in hepatic impairment: Monitoring of plasma levels is recommended because of significantly increased half-life.

When transferring from another antiarrhythmic agent, allow for 2-4 half-lives of the agent to pass before initiating flecainide therapy.

Dairy products (milk, infant formula, yogurt) may interfere with the absorption of flecainide in infants; there is one case report of a neonate (GA 34 weeks PNA >6 days) who required extremely large doses of oral flecainide when administered every 8 hours with feedings ("milk feeds"); changing the feedings from "milk feeds" to 5% glucose feeds alone resulted in a doubling of the flecainide serum concentration and toxicity; clearance of flecainide may be decreased in patients with strict vegetarian diets due to urinary pH greater than or equal to 8

EKG, blood pressure, pulse, periodic serum concentrations, especially in patients with renal or hepatic impairment

Therapeutic: 0.2-1 mg/mL; pediatric patients may respond at the lower end of the recommended therapeutic range

Flecainide is a Class Ic antiarrhythmic with a very narrow therapeutic index and with considerable proarrhythmic properties. The CAST trial, evaluating flecainide in the treatment of asymptomatic ventricular extrasystoles after myocardial infarction, showed a significant increase in mortality. In lower doses, flecainide has sometimes been used for maintenance of sinus rhythm in patients with severe refractory atrial fibrillation, without structural heart disease.

Dizziness is common; may cause sedation; may rarely cause nervousness

Use beta-blockers with caution; may produce additive negative inotropic effect; use caution with TCAs; may affect cardiac conduction; CYP2D6 substrate; use caution with the SSRIs

No information available to require special precautions

No effects or complications reported

Take exactly as directed, around-the-clock. Do not discontinue without consulting prescriber. You will require frequent monitoring while taking this medication. You may experience lightheadedness, nervousness, dizziness, visual disturbances (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or nausea, vomiting, or loss of appetite (small frequent meals may help). Report palpitations, chest pain, excessively slow or rapid heartbeat; acute nervousness, headache, or fatigue; unusual weight gain; unusual cough; difficulty breathing; swelling of hands or ankles; or muscle tremor, numbness, or weakness. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

Administer around-the-clock rather than 4 times/day, 3 times/day, etc, (ie, 12-6-12-6, not 9-1-5-9) to promote less variation in peak and trough serum levels

Monitor EKG and serum concentrations

Tablet, as acetate: 50 mg, 100 mg, 150 mg

A 5 mg/mL suspension compounded from tablets and an oral flavored commercially available diluent (Roxane®) was stable for up to 45 days when stored at 5°C or 25°C in amber glass bottles. Flecainide 20 mg/mL was found stable for up to 60 days at 5°C and 25°C in a 1:1 preparation of Ora-Sweet® and Ora-Plus®, in Ora-Sweet® SF and Ora-Plus® and in cherry syrup

Wiest DB, Garner SS, and Pagacz LR, "Stability of Flecainide Acetate in an Extemporaneously Compounded Oral Suspension," Am J Hosp Pharm, 1992, 49(6):1467-70.

Borgeat A, Biollaz J, Freymond B, et al, "Hemofiltration Clearance of Flecainide in a Patient With Acute Renal Failure," Intensive Care Med, 1988, 14(3):236-7.

Fenrich AL Jr, Perry JC, and Friedman RA, "Flecainide and Amiodarone: Combined Therapy for Refractory Tachyarrhythmias in Infants," J Am Coll Cardiol, 1995, 25(5):1195-8.

Gotz D, Pohle S, and Barckow D, "Primary and Secondary Detoxification in Severe Flecainide Intoxication," Intensive Care Med, 1991, 17(3):181-4.

Muhiddin KA, Johnston A, and Turner P, "The Influence of Urinary pH on Flecainide Excretion and Its Serum Pharmacokinetics," Br J Clin Pharmacol, 1984, 17(4):447-51.

Musto B, Cavallaro C, Musto A, et al, "Flecainide Single Oral Dose for Management of Paroxysmal Supraventricular Tachycardia in Children and Young Adults," Am Heart J, 1992, 124(1):110-5.

Perry JC and Garson A Jr, "Flecainide Acetate for Treatment of Tachyarrhythmias in Children: Review of World Literature on Efficacy, Safety, and Dosing," Am Heart J, 1992, 124(6):1614-21.

Perry JC, McQuinn RL, Smith RT Jr, et al, "Flecainide Acetate for Resistant Arrhythmias in the Young: Efficacy and Pharmacokinetics," J Am Coll Cardiol, 1989, 14(1):185-91.

Priestley KA, Ladusans EJ, Rosenthal E, et al, "Experience With Flecainide for the Treatment of Cardiac Arrhythmias in Children," Eur Heart J, 1988, 9(12):1284-90.

Russell GA and Martin RP, "Flecainide Toxicity," Arch Dis Child, 1989, 64(6):860-2.

Salerno DM, Murakami MM, Johnston RB, et al, "Reversal of Flecainide-Induced Ventricular Arrhythmia by Hypertonic Sodium Bicarbonate in Dogs," Am J Emerg Med, 1995, 13(3):285-93.

Vanderhal AL, Cocjin J, Santulli TV Jr, et al, "Conjugated Hyperbilirubinemia in a Newborn Infant After Maternal (Transplacental) Treatment With Flecainide Acetate For Fetal Tachycardia and Fetal Hydrops," J Pediatr, 1995, 126(6):988-90.

Winkelmann BR and Leinberger H, "Life-Threatening Flecainide Toxicity. A Pharmacodynamic Approach," Ann Intern Med, 1987, 106(6):807-14.

Zeigler V, Gillette PC, Ross BA, et al, "Flecainide for Supraventricular and Ventricular Arrhythmias in Children and Young Adults," Am J Cardiol, 1988, 62(10 Pt 1):818-20.