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 an MI more than 6 days but less than 2 years previously. An excessive mortality or nonfatal 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 5.1% for flecainide and 2.3% for the matched placebo. The average duration of treatment with flecainide in this study was 10 months.
The applicability of the CAST results to other populations (eg, those without recent MI) is uncertain, but at present, it is prudent to consider the risks of Class ΙC 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.
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% of these patients. Of 19 patients in the literature with chronic atrial fibrillation (CAF), 10.5% experienced ventricular tachycardia (VT) or ventricular fibrillation (VF). Flecainide is not recommended for use in patients with CAF. Case reports of ventricular proarrhythmic effects in patients treated with flecainide for atrial fibrillation/flutter have included increased premature ventricular contractions (PVCs), VT, VF, and death.
As with other Class Ι 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.
Fetal tachycardia, sustained (maternal/transplacental administration) (off-label use): Oral: 100 to 300 mg/day in divided doses administered every 8 to 12 hours (AHA [Donofrio 2014]). Adjust dose to fetal response. Some studies targeted maternal blood levels between 0.2 and 1 mcg/mL. Maximum dose: 450 mg/day (Alsaied 2017).
Paroxysmal atrial fibrillation/flutter and paroxysmal supraventricular tachycardias (prevention): Oral: Initial: 50 mg every 12 hours; increase by 50 mg twice daily at 4-day intervals; maximum dose: 300 mg/day. The AHA/ACC/HRS atrial fibrillation guidelines recommend a maximum dose of 400 mg/day (AHA/ACC/HRS [January 2014]).
Ventricular arrhythmias (prevention): Oral: Initial: 50 to 100 mg every 12 hours; increase by 50 mg twice daily at 4-day intervals; maximum: 400 mg/day (AHA/ACC/HRS [Al-Khatib 2017]; Benhorin 2000; Chorin 2018; van der Werf 2011; Watanabe 2013). Some patients inadequately controlled with or intolerant to dosing every 12 hours may require dosing every 8 hours. Note: Initiate therapy in a hospital setting in patients with sustained ventricular tachycardia. 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.
Ventricular premature beats (off-label use) : Oral: 50 to 200 mg every 12 hours (AHA/ACC/HRS [Al-Khatib 2017]). According to the prescribing information, may increase by 50 mg twice daily at 4-day intervals; maximum: 400 mg/day.
Atrial fibrillation or flutter (pharmacological cardioversion) (off-label dose): Oral: Note: May be used on an outpatient basis (“Pill-in-the-pocket”). An initial inpatient cardioversion trial should have been successful before sending patient home on this approach. Patient must be taking an AV nodal-blocking agent (eg, beta-blocker, nondihydropyridine calcium channel blocker) prior to initiation of antiarrhythmic (AHA/ACC/HRS [January 2014]; Alboni 2004).
<70 kg: 200 mg; may not repeat in ≤24 hours
≥70 kg: 300 mg; may not repeat in ≤24 hours
Conversion from another antiarrhythmic agent: Allow for 2 to 4 half-lives of the other agent after discontinuation to pass before initiating flecainide therapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Flecainide has a narrow therapeutic index, and the half-life is prolonged in patients with kidney impairment. In patients with kidney impairment, monitor serum trough concentrations (especially in patients with CrCl ≤35 mL/minute/1.73 m2) and ECG parameters frequently following initiation of therapy or dose adjustments and periodically during therapy (Tamargo 2015; expert opinion).
No dosage adjustment is likely to be necessary for pharmacological cardioversion of atrial fibrillation or flutter “pill-in-the-pocket” dosing, as use of this approach should be infrequent enough to avoid accumulation (expert opinion).
Altered kidney function:
CrCl ≥60 mL/minute/1.73 m2: No dosage adjustment necessary (expert opinion).
CrCl >35 to <60 mL/minute/1.73 m2: Initial: No dosage adjustment necessary; consider obtaining serum trough concentrations to guide dosage adjustments in addition to the anticipated clinical response; dose increases should be made cautiously and at intervals of ~7 days (Forland 1988; manufacturer's labeling; expert opinion).
CrCl ≤35 mL/minute/1.73 m2: Initial: Administer 50% of the usual indication-specific initial dose in 1 to 2 divided doses (manufacturer's labeling; expert opinion); subsequent dose adjustments should preferentially be determined based on serum trough concentrations in addition to the anticipated clinical response; the manufacturer's labeling recommends not to use flecainide if monitoring of trough concentrations is not available in patients with severe impairment (manufacturer's labeling; expert opinion); dose increases should be made no more frequently than every 7 days (Forland 1988).
Hemodialysis, intermittent (thrice weekly): Not dialyzable (manufacturer's labeling): Note: Use with extreme caution. In a retrospective evaluation of 5 dialysis patients receiving chronic flecainide therapy, significant variability (>7-fold) of dose-corrected steady-state plasma concentrations was observed (Evers 1994).
Initial: Administer 50% of the usual indication-specific initial dose in 1 to 2 divided doses (manufacturer's labeling; expert opinion); subsequent dose adjustments should preferentially be determined based on serum trough concentrations in addition to the anticipated clinical response; the manufacturer's labeling recommends not to use flecainide if monitoring of trough concentrations is not available in patients with severe kidney impairment (Evers 1994; manufacturer's labeling; expert opinion); dose increases should be made no more frequently than every 7 days (Forland 1988; expert opinion).
Peritoneal dialysis: Not dialyzable (Bailie 1988): Note: Use with extreme caution. In a retrospective evaluation of 5 dialysis patients receiving chronic flecainide therapy, extreme variability (>7-fold) of dose-corrected steady-state plasma concentrations was observed (Evers 1994).
Initial: Administer 50% of the usual indication-specific initial dose in 1 to 2 divided doses (manufacturer's labeling; expert opinion); subsequent dose adjustments should preferentially be determined based on serum trough concentrations in addition to the anticipated clinical response; the manufacturer's labeling recommends not to use flecainide if monitoring of trough concentrations is not available in patients with severe kidney impairment (Evers 1994; manufacturer's labeling; expert opinion); dose increases should be made no more frequently than every 7 days (Forland 1988; expert opinion).
CRRT: Not significantly removed (Borgeat 1988):
Initial: Administer 50% of the usual indication-specific initial dose in 1 to 2 divided doses (manufacturer's labeling; expert opinion); subsequent dose adjustments should preferentially be determined based on serum trough concentrations in addition to the anticipated clinical response; the manufacturer's labeling recommends not to use flecainide if monitoring of trough concentrations is not available in patients with severe kidney impairment (manufacturer's labeling; expert opinion); dose increases should be made no more frequently than every 7 days (Forland 1988; expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): Not likely to be significantly removed (expert opinion):
Initial: Administer 50% of the usual indication-specific initial dose in 1 to 2 divided doses (manufacturer's labeling; expert opinion); subsequent dose adjustments should preferentially be determined based on serum trough concentrations in addition to the anticipated clinical response; the manufacturer's labeling recommends not to use flecainide if monitoring of trough concentrations is not available in patients with severe kidney impairment (manufacturer's labeling; expert opinion); dose increases should be made no more frequently than every 7 days (Forland 1988; expert opinion).
There are no dosage adjustments provided in the manufacturer’s labeling; however elimination from the plasma may be slower in patients with hepatic impairment. Use with caution; obtain plasma concentrations to guide dosage adjustments. Dose increases should be made very cautiously at intervals >4 days and serum concentrations monitored frequently. Frequent plasma level monitoring is required in patients with severe hepatic impairment; if unavailable, use is not recommended.
(For additional information see "Flecainide: Pediatric drug information")
Arrhythmias:
BSA-directed dosing: Use caution with dose titration, as small change in dose may result in disproportionate increase in plasma concentrations.
Infants ≤6 months: Oral: Initial: 50 mg/m2/day divided every 8 to 12 hours; may titrate dose at 4-day intervals; maximum daily dose: 200 mg/m2/day; higher doses have been associated with an increased risk of proarrhythmic effects.
Infants >6 months, Children, and Adolescents: Oral: Initial: 100 mg/m2/day divided every 8 to 12 hours; may titrate dose at 4-day intervals; maximum daily dose: 200 mg/m2/day; higher doses have been associated with an increased risk of proarrhythmic effects.
Weight-based dosing: Limited data available; dosing regimens variable: Infants, Children, and Adolescents: Oral: Initial: 1 to 3 mg/kg/day divided every 8 hours; may titrate dose at 4-day intervals; usual maintenance range: 3 to 6 mg/kg/day (Park 2014); an average effective dose of 4 mg/kg/day was reported in an expert analysis of literature and clinical experience (Perry 1992); maximum daily dose: 8 mg/kg/day (Perry 1992); higher doses have been associated with an increased risk of proarrhythmic effects.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric specific recommendations; based on experience in adult patients, dosage adjustment suggested.
There are no dosage adjustments provided in the manufacturer's labeling; however, elimination from the plasma may be slower in patients with hepatic impairment. Use with caution; obtain plasma concentrations to guide dosage adjustments. Dose increases should be made very cautiously at intervals >4 days and serum concentrations monitored frequently. Frequent plasma level monitoring is required in patients with severe hepatic impairment; if unavailable, use is not recommended.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as acetate:
Generic: 50 mg, 100 mg, 150 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as acetate:
Tambocor: 50 mg, 100 mg
Generic: 50 mg, 100 mg
Oral: When used for the management of fetal tachycardia (maternal/transplacental administration; off-label use), oral doses are administered to the mother.
Oral: Administer around-the-clock to promote less variation in peak and trough serum levels. May be administered in children without regard to food; however, administration with milk or milk-based formulas may decrease absorption; monitor serum concentrations closely with any changes in milk or milk-based formula consumption; dose adjustments may be necessary (Russel 1989; Thompson 2012; manufacturer's labeling).
Paroxysmal atrial fibrillation/flutter and paroxysmal supraventricular tachycardias (prevention): Prevention of paroxysmal atrial fibrillation/flutter associated with disabling symptoms and paroxysmal supraventricular tachycardias (PSVT), including atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, and other supraventricular tachycardias of unspecified mechanism associated with disabling symptoms in patients without structural heart disease.
Guideline recommendations: Due to safety risks, flecainide should be reserved for symptomatic supraventricular tachycardias (SVTs) in patients without structural or ischemic heart disease who are not candidates for, or prefer not to undergo, catheter ablation and in whom other therapies have failed or are contraindicated (ACC/AHA/HRS [Page 2015]).
Ventricular arrhythmias (prevention): Prevention of documented life-threatening ventricular tachyarrhythmias (eg, sustained ventricular tachycardia) in patients without structural heart disease.
Guideline recommendations: Flecainide is an appropriate adjunctive therapy in patients with type 3 long QT syndrome or catecholaminergic polymorphic ventricular tachycardia who are already taking a maximally tolerated beta-blocker but still experiencing symptoms (AHA/ACC/HRS [Al-Khatib 2017]; Benhorin 2000; Chorin 2018; Van der Werf 2011; Watanabe 2013)
Limitations of use: Use of flecainide is not recommended in patients with less severe ventricular arrhythmias, even if symptomatic. Because of the proarrhythmic effects of flecainide, its use should be reserved for patients in whom the benefits of treatment outweigh the risks. Flecainide should not be used in patients with permanent atrial fibrillation (not adequately studied) or recent myocardial infarction. No evidence from controlled trials have demonstrated favorable effects of flecainide on survival or the incidence of sudden death.
Atrial fibrillation or flutter (pharmacologic cardioversion); Fetal tachycardia, sustained; Ventricular premature beats
Flecainide may be confused with fluconazole
Tambocor [DSC] may be confused with Pamelor, Temodar, tamoxifen, Tamiflu
Potentially fatal proarrhythmic effects (including ventricular premature contractions, ventricular tachycardia, and ventricular fibrillation) have been reported in patients with atrial fibrillation without structural heart disease who received flecainide (Ref). Additionally, prolongation of P-R interval on ECG, widened QRS complex on ECG, and prolonged QT interval on ECG, atrioventricular block, or right bundle branch block are possible, leading to sinus bradycardia, sinus pause, sinoatrial arrest, or torsades de pointes (Ref). The incidence of proarrhythmic effects with flecainide use is lower in patients without structural heart disease (Ref); one study noted a <3% incidence of sustained ventricular arrhythmia (Ref).
Mechanism: Dose-related; related to the pharmacologic action; flecainide may unmask the ECG pattern of Brugada syndrome, thereby inducing ventricular tachycardia (Ref). Additionally, flecainide may promote reentry in ventricular tissue via inhibition of rapid sodium channels (slowing phase 0) and inhibition of the slow calcium channel (Ref). Sodium channel blockade also slows conduction through all cardiac conduction pathways, leading to widened QRS, bundle branch block, and prolonged PR interval (Ref).
Onset: Varied; most patients experience proarrhythmic effects or conduction disturbances within the first 1 to 3 weeks of therapy (Ref). Another study reported events within the 12-week period of treatment (Ref).
Risk factors:
• Large dose escalations (Ref)
• Sick sinus syndrome (or other sinus node dysfunction) (Ref)
• Sustained ventricular tachycardia (Ref)
• Atrioventricular conduction abnormalities (Ref)
When treating atrial fibrillation or atrial flutter, 1:1 atrioventricular (AV) conduction may occur, resulting in a rapid ventricular rate and hemodynamic compromise (Ref). The conduction is reversible with cardioversion (Ref).
Mechanism: Related to the pharmacologic action; the effects of flecainide on rhythm allow for the organization of atrial fibrillation into atrial flutter. Additionally, flecainide slows conduction through sodium channel blockade, resulting in a slower atrial flutter rate, facilitating 1:1 conduction through the AV node (Ref).
Onset: Rapid; symptoms associated with 1:1 conduction occur within 30 minutes to a few hours after a dose (Ref).
Risk factors:
• Physical activity after a dose (Ref)
• Dual AV conduction pathways (Ref)
• Absence of AV nodal blocking agent (eg, beta blocker, non-dihydropyridine calcium channel blocker, digoxin) used concurrently (Ref)
Flecainide use in patients with structural heart disease (SHD) (heart failure, myocardial infarction/ischemia) may exacerbate proarrhythmic events (eg, ventricular arrhythmias) and increase the risk of death (Ref). Acute decompensated worsening of heart failure is possible in patients with chronic heart failure (Ref).
Mechanism: Related to the pharmacologic action. In ischemic tissue, flecainide causes significant rate-dependent slowing of conduction via sodium channel inhibition, leading to heterogeneous conduction and reentry pathways (Ref). Flecainide also exhibits significant negative inotropic properties, which can significantly impact patients with poor cardiac function at baseline (Ref).
Onset: Varied. For patients with heart failure with reduced ejection fraction, flecainide significantly increased the risk of decompensation over a 1-year follow-up (Ref). In the CAPS study, an onset of ~3 months was suggested based on the Kaplan Meier curve for percent free from new or worsening heart failure (Ref). In the CAST trial, patients were followed up to 10 months; cardiac events and death began nearly immediately after initiation of flecainide and continued to occur over the 10-month period (Ref).
Risk factors:
• Myocardial infarction (Ref)
• Chronic heart failure (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Ventricular arrhythmia (new or exacerbated: 7% to 13%)
Nervous system: Dizziness (19%)
Ophthalmic: Visual disturbances (16%; including accommodation disturbance, blurred vision, seeing spots)
1% to 10%:
Cardiovascular: Bradycardia (1%), cardiac arrhythmia (new or worsened: 1% to 7%), cardiac failure (≤9%), chest pain (5%), edema (4%), flushing (1% to 3%), palpitations (6%), sinoatrial arrest (1% to 3%), sinus bradycardia (≤1%), sinus pause (1% to 3%), syncope (1% to 3%), tachycardia (1% to 3%), worsening of heart failure (≤9%)
Dermatologic: Diaphoresis (1% to 3%), skin rash (1% to 3%)
Gastrointestinal: Abdominal pain (3%), anorexia (1% to 3%), constipation (4%), diarrhea (1% to 3%), dyspepsia (1% to 3%), nausea (9%), vomiting (1% to 3%)
Nervous system: Anxiety (1% to 3%), ataxia (1% to 3%), depression (1% to 3%), drowsiness (1% to 3%), fatigue (8%), headache (10%), hypoesthesia (1% to 3%), insomnia (1% to 3%), malaise (1% to 3%), paresis (1% to 3%), paresthesia (1% to 3%), vertigo (1% to 3%)
Neuromuscular & skeletal: Asthenia (5%), tremor (5%)
Ophthalmic: Diplopia (1% to 3%)
Otic: Tinnitus (1% to 3%)
Respiratory: Dyspnea (10%)
Miscellaneous: Fever (1% to 3%)
<1%:
Cardiovascular: Angina pectoris, complete atrioventricular block, hypertension, hypotension, second degree atrioventricular block
Dermatologic: Alopecia, exfoliative dermatitis, pruritus, urticaria
Endocrine & metabolic: Decreased libido
Gastrointestinal: Dysgeusia, flatulence, swelling of lips, swelling of mouth, swollen tongue, xerostomia
Genitourinary: Impotence, urinary retention
Hematologic & oncologic: Granulocytopenia, leukopenia, thrombocytopenia
Nervous system: Abnormal dreams, amnesia, apathy, confusion, depersonalization, euphoria, neuropathy, seizure, speech disturbance, stupor, twitching
Neuromuscular & skeletal: Arthralgia, myalgia
Ophthalmic: Eye irritation, eye pain, nystagmus disorder, photophobia
Renal: Polyuria
Respiratory: Bronchospasm, pneumonitis, pulmonary infiltrates
Frequency not defined: Cardiovascular: Bundle branch block, prolongation of J-T interval on ECG, prolongation P-R interval on ECG (Echt 2020), torsades de pointes (Echt 2020), widened QRS complex on ECG (Echt 2020)
Postmarketing:
Cardiovascular: Exacerbation of cardiac arrhythmias (Echt 2020), prolonged QT interval on ECG (Echt 2020), supraventricular cardiac arrhythmias (Echt 2020), ventricular fibrillation (Echt 2020), ventricular premature contractions (Echt 2020), ventricular tachyarrhythmia (Echt 2020), ventricular tachycardia (Echt 2020), wide complex tachycardia (Echt 2020)
Hepatic: Increased serum alkaline phosphatase, increased serum transaminases
Hypersensitivity to flecainide or any component of the formulation; 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; concurrent use of ritonavir
According to the American College of Cardiology/American Heart Association/European Society of Cardiology, the use of flecainide is considered contraindicated in patients with structural heart disease (ACC/AHA/HRS [Page 2015]; AHA/ACC/HRS [Al-Khatib 2017])
Disease-related concerns:
• AV block: If second- or third-degree AV block, or right bundle branch block associated with a left hemiblock occur, flecainide therapy should be discontinued unless a temporary or implanted ventricular pacemaker is in place to ensure an adequate ventricular rate.
• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.
• Hepatic impairment: Use with caution in patients with significant hepatic impairment; benefit should outweigh risk. Consider careful monitoring during initiation of therapy. Dose titration should occur only after steady state has been achieved (≥4 days after initiation). Frequent plasma level monitoring is required in patients with severe hepatic impairment; if unavailable, use is not recommended.
• Renal impairment: Use with caution in patients with significant renal impairment. Frequent plasma level monitoring is required in patients with severe renal impairment; if unavailable, use is not recommended.
• Structural or ischemic heart disease: According to the manufacturer, use with extreme caution in patients with structural heart disease as the risk of death and cardiac events may be increased. Avoid use in patients with structural or ischemic heart disease (ACC/AHA/HRS [Page 2015]).
Special populations:
• Pediatric: Small changes in dose may lead to disproportionate increases in plasma concentrations in pediatric patients. Following initiation of therapy or changes in dose, obtain plasma trough concentrations and ECG once steady state has been achieved (>5 doses after initiation or change); regular monitoring of trough concentrations and ECG is recommended by the manufacturer during the first year of therapy and during major changes in dietary milk intake as milk may interfere with the absorption of flecainide in pediatric patients (Russell 1989; Thompson 2012; manufacturer's labeling); consider dose reductions when milk is removed from the diet (eg, during weaning or bouts of gastroenteritis).
Other warnings/precautions:
• Pacemakers: Use with caution in patients with permanent pacemakers or temporary pacing wires; can increase endocardial pacing thresholds and suppress ventricular escape rhythms. Do not use in patients with existing poor thresholds or nonprogrammable pacemakers unless suitable pacing rescue is available. The pacing threshold in patients with pacemakers should be determined at baseline, 1 week after initiation and at regular intervals thereafter.
Substrate of CYP1A2 (minor), CYP2D6 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amiodarone: May enhance the QTc-prolonging effect of Flecainide. Amiodarone may increase the serum concentration of Flecainide. Management: Decrease flecainide dose by 50%. Monitor for QTc interval prolongation and ventricular arrhythmias, and consider monitoring for elevated flecainide concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Antihepaciviral Combination Products: May increase the serum concentration of Flecainide. Management: Canadian labeling recommends avoiding this combination. Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Asunaprevir: May increase the serum concentration of Flecainide. Risk X: Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May decrease the excretion of Flecainide. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Flecainide. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Flecainide. Risk C: Monitor therapy
Dabrafenib: May enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Digoxin: Flecainide may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Etravirine: May decrease the serum concentration of Flecainide. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with MATE1/2-K substrates when possible. If combined, monitor for increased MATE1/2-K substrate toxicities. Risk D: Consider therapy modification
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Fluorouracil Products: QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Haloperidol: QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Lacosamide: QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May increase the serum concentration of Flecainide. Risk X: Avoid combination
Ondansetron: QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
PAZOPanib: QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of PAZOPanib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Pentamidine (Systemic): QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Pindolol: Flecainide may enhance the bradycardic effect of Pindolol. The negative inotropic effects of Pindolol may also be enhanced. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of other QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Quinidine (Non-Therapeutic): May enhance the QTc-prolonging effect of QT-prolonging CYP2D6 Substrates. Quinidine (Non-Therapeutic) may increase the serum concentration of QT-prolonging CYP2D6 Substrates. Risk X: Avoid combination
Risdiplam: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of risdiplam with MATE substrates if possible. If the combination cannot be avoided, monitor closely for adverse effects. Consider a reduced dose of the MATE substrate according to that substrate's labeling if appropriate. Risk D: Consider therapy modification
RisperiDONE: May enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ritonavir: May increase the serum concentration of Flecainide. Risk X: Avoid combination
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Simeprevir: May increase the serum concentration of Flecainide. Risk C: Monitor therapy
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Sodium Bicarbonate: May increase the excretion of Flecainide. Sodium Bicarbonate may increase the serum concentration of Flecainide. Risk C: Monitor therapy
Sodium Lactate: May decrease the excretion of Flecainide. Risk C: Monitor therapy
Tafenoquine: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of MATE substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the MATE substrate and consider a reduced dose of the MATE substrate according to that substrate's labeling. Risk D: Consider therapy modification
Tipranavir: May increase the serum concentration of Flecainide. Risk X: Avoid combination
Tobacco (Smoked): May decrease the serum concentration of Flecainide. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Tromethamine: May decrease the excretion of Flecainide. Risk C: Monitor therapy
Verapamil: May enhance the adverse/toxic effect of Flecainide. In particular, this combination may significantly impair myocardial contractility and AV nodal conduction. Risk C: Monitor therapy
Clearance may be decreased in patients following strict vegetarian diets due to urinary pH ≥8. Milk may interfere with the absorption of flecainide (Russell 1989; Thompson 2012). Management: Dose reduction should be considered when milk is removed from the diet (eg, during weaning or bouts of gastroenteritis). Plasma trough flecainide levels should be monitored during major changes in dietary milk intake.
Flecainide crosses the placenta (Palmer 1990). Placental transfer is not decreased when fetal hydrops is present. Neonatal conduction abnormalities have been reported (AHA [Donofrio 2014]).
Untreated maternal arrhythmias may cause adverse events in the mother and fetus. Flecainide may be used for the ongoing management of pregnant women with highly symptomatic supraventricular tachycardia (SVT). The lowest effective dose is recommended; avoid use during the first trimester if possible (ACC/AHA/HRS [Page 2015]). Use is also recommended for the prevention of SVT in patients with Wolff-Parkinson-White (WPW) syndrome. Until more information is available, when prevention of SVT in patients without WPW syndrome, atrial tachycardia, or atrial fibrillation is needed in pregnancy, flecainide is generally reserved for use when other agents are not effective (ESC [Regitz-Zagrosek 2018]).
Flecainide (administered maternally) may be considered for the in utero management of fetal SVT or atrial flutter with hydrops or ventricular dysfunction. Flecainide may also be considered for SVT without hydrops or ventricular dysfunction if heart rate is ≥200 bpm, or other rare tachycardias with an average heart rate of ≥200 bpm. In addition, flecainide may be considered for fetal ventricular tachycardia (VT) with normal QTc with or without hydrops but is contraindicated for the treatment of fetal VT when long QT syndrome is suspected or confirmed (AHA [Donofrio 2014]).
Flecainide is present in breast milk (McQuinn 1990; Wagner 1990).
The relative infant dose (RID) of flecainide is 8% when calculated using the highest average breast milk concentration located and compared to a weight-adjusted maternal dose of 200 mg/day.
In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
The RID of flecainide was calculated using a milk concentration of 1,529 ng/mL, providing an estimated daily infant dose via breast milk of 0.23 mg/kg/day. This milk concentration was obtained following maternal administration of oral flecainide 100 mg twice daily for 5 days to 11 lactating females, beginning the first day postpartum. The average daily flecainide concentrations in breast milk, and the maternal plasma trough concentrations were variable between subjects; however, the milk/plasma ratio was consistent across the group. Concentrations of flecainide in breast milk were as high as 4 times those in the maternal serum. Based on data from this study, milk concentrations would decline at approximately the same rate as maternal serum concentrations once the medication is discontinued (McQuinn 1990).
ECG, BP, heart rate, periodic serum trough concentrations, especially in patients with renal or hepatic impairment, concomitant administration of amiodarone and pediatric patients.
Therapeutic: Trough concentration: 0.2 to 1 mcg/mL. Note: Pediatric patients may respond at the lower end of the recommended therapeutic range (0.2 to 0.5 mcg/mL) but up to 0.8 mcg/mL may be required.
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: Nearly complete; may be decreased when administered with milk in pediatric patients (Thompson 2012; manufacturer's labeling).
Protein binding: ~40%.
Half-life elimination:
Newborns: Up to ≤29 hours; 3 months: 11 to 12 hours; 12 months: 6 hours.
Children: ~8 hours.
Adolescents 12 to 15 years: ~11 to 12 hours.
Adults: ~20 hours (range: 12 to 27 hours); increased in patients with heart failure (NYHA Class III) or renal dysfunction.
Time to peak, serum: ~3 hours (range: 1 to 6 hours).
Excretion: Urine (30% [range: 10% to 50%] as unchanged drug); feces (5%).
Altered kidney function: In patients with end-stage kidney disease, renal clearance is very low as compared to patients with moderate kidney impairment, and the plasma half-life may extend up to 58 hours (Conard 1984).
Tablets (Flecainide Acetate Oral)
50 mg (per each): $1.74 - $2.56
100 mg (per each): $2.73 - $4.01
150 mg (per each): $3.76 - $5.52
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