Dosing and uses of Tambocor (flecainide)
Adult dosage forms and strengths
tablet
- 50mg
- 100mg
- 150mg
Arrhythmias
PSVT and paroxysmal atrial fibrillation
- 50 mg PO BID; may increase by 50 mg every 4 days; do not exceed 300 mg/day
Sustained Vt
- 100 mg PO BID initiated in hospital; may increase by 50 mg every 4 days; do not exceed 400 mg/day
Dosing Considerations
Steady-state plasma levels not achieved for 3-5 days, so increases in dosage should not be made less than every 4 days
Loading dose not recommended, due to increased incidence of proarrhythmic events and CHF
Patients intolerant to BID dosing may require 8hr dosing
Once adequate control of arrhythmia has been achieved, may reduce dose, provided there is no loss of efficacy
After 5 doses/steady state, obtain ECG after initiation or change of dose; obtain plasma trough flecainide levels 1 hour predose
Usual trough plasma levels: 0.2-1 mcg/mL
When given concomitantly with amiodarone, reduce flecainide dose by 50% and monitor closely
Dose cautiously in patients with history of MI or CHF
When switching from another antiarrhythmic to flecainide, allow >2-4 plasma half-lives to elapse before starting flecainide; if discontinuation of previous drug may produce life-threatening arrhythmias, consider hospitalizing patient
Dosage modifications
Renal impairment
- Severe (<35 mL/min): 100 mg PO qDay or 50 mg PO BID
- >25 mL/min: 100 mg PO BID
Hepatic impairment
- Use only if benefits outweigh risk; monitor plasma levels regularly; reduce dose as necessary
Narcolepsy (Orphan)
Orphan designation of a fixed dose combination of modafinil and flecainide for narcolepsy
Sponsor
- Theranexus SA; 86 Rue de Paris; Orsay, France
Pediatric dosage forms and strengths
tablet
- 50mg
- 100mg
- 150mg
Arrhythmias
<6 months: 50 mg/m²/day PO divided q8-12hr
≥6 months: 100 mg/m²/day PO divided q8-12hr
Not to exceed 200 mg/m²/day
Dosing Considerations
Usual therapeutic level: 200-500 ng/mL; some may require <800 ng/mL for adequate controL
Steady-state plasma levels not achieved for 3-5 days, so increases in dosage should not be made less than every 4 days
Loading dose not recommended, due to increased incidence of proarrhythmic events and CHF
Patients intolerant to BID dosing may require 8hr dosing
Once adequate control of arrhythmia has been achieved, may reduce dose, provided there is no loss of efficacy
After 5 doses/steady state, obtain ECG after initiation or change of dose; obtain plasma trough flecainide levels 1 hour predose
Usual trough plasma levels: 0.2-1 mcg/mL
When given concomitantly with amiodarone, reduce flecainide dose by 50% and monitor closely
Dose cautiously in patients with history of MI or CHF
When switching from another antiarrhythmic to flecainide, allow >2-4 plasma half-lives to elapse before starting flecainide; if discontinuation of previous drug may produce life-threatening arrhythmias, consider hospitalizing patient
Dosage modifications
Renal impairment
- Severe (<35 mL/min): 100 mg PO qDay or 50 mg PO BID
- >25 mL/min: 100 mg PO BID
Hepatic impairment
- Use only if benefits outweigh risk; monitor plasma levels regularly; reduce dose as necessary
Tambocor (flecainide) adverse (side) effects
>10%
Visual disturbances (5-16%)
Dizziness (10-19%)
1-10%
Arrhythmias
Edema (1-4%)
Asthenia (2-5%)
Palpitations (2-7%)
Fatigue (3-8%)
Tremors (2-5%)
Constipation (1-4%)
Nausea (5-9%)
Chest pain (1-5%)
Dyspnea (5-10%)
Headache (5-10%)
Abdominal pain (1-3%)
Malaise (1-3%)
Fever (1-3%)
Tachycardia (1-3%)
Sinus pause/arrest (1-3%)
Vomiting (1-3%)
Diarrhea (1-3%)
Dyspepsia (1-3%)
Anorexia (1-3%)
Rash (1-3%)
Diplopia (1-3%)
Hypoesthesia (1-3%)
Paresthesia (1-3%)
Paresis (1-3%)
Ataxia (1-3%)
Flushing (1-3%)
Diaphoresis (1-3%)
Vertigo (1-3%)
Syncope (1-3%)
Somnolence (1-3%)
Tinnitus (1-3%)
Anxiety (1-3%)
Insomnia (1-3%)
Depression (1-3%)
Warnings
Black box warnings
Mortality
- NHLBI’s Cardiac Arrhythmia Suppression Trial (CAST): Excessive mortality or nonfatal cardiac arrest (7.7%) shown with encainide or flecainide, compared with placebo (3%)
- This was a long-term, multicenter, randomized, double-blind study in patients with asymptomatic, non-life-threatening ventricular arrhythmias who previously had MI >6 days but <2 yr
- Average duration of treatment with encainide or flecainide was 10 months
- Applicability of results to other populations is uncertain
- Reserve class IC antiarrhythmics use for life-threatening ventricular arrhythmias only
- Due to known proarrhythmic properties of flecainide and lack of evidence of improved survival for any antiarrhythmics, flecainide use should be restricted to patients with life-threatening ventricular arrhythmias
Ventricular proarrhythmic effects with AF/flutter
- Not recommended for chronic atrial fibrillation
- 10.5% incidence of ventricular tachycardia/fibrillation in patients treated for chronic atrial fibrillation
- Proarrhythmic effects with flecainide for atrial fibrillation/flutter: Increased risk of PVCs, ventricular tachycardia, ventricular fibrillation, and fatality
- As with other class I agents, use of flecainide for atrial flutter has been reported with 1:1 atrioventricular conduction due to atrial rate slowing
- Paradoxical increase in ventricular rate may occur in patients with atrial fibrillation; concomitant negative chronotropic therapy (eg, digoxin, beta blockers) may lower risk
Contraindications
Hypersensitivity
2nd or 3rd degree AV block, right bundle branch block when associated with left hemiblock (bifascicular block), unless pacemaker is present to sustain cardiac rhythm; discontinue therapy immediately
Cautions
Atrial fibrillation, CHF, hypotension, HTN, post MI patients, geriatrics, proarrhythmia events, hepatic/renal impairment, sick sinus syndrome
May slow cardiac conduction to produce dose-related increases in PR, QRS, and QT intervals; manage patient on lowest effective dose
Discontinuation should be done in hospitaL
Causes increased mortality in post-AMI period, also with chronic atrial fibrillation
May affect endocardial pacemaker reversibly by increasing endocardial pacing thresholds or suppressing ventricular escape rhythms; do not administer to patients with existing poor thresholds or nonprogrammable pacemakers unless suitable pacing rescue is available
Correct preexisting hypokalemia or hyperkalemia before initiating therapy
May cause visual disturbances
Flecainide may depress LV function significantly with preexisting LV dysfunction
Flecainide should be avoided in patients with HF or structural heart disease.
Pregnancy and lactation
Pregnancy category: C
Lactation: Enters breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tambocor (flecainide)
Mechanism of action
Class IC antidysrhythmic; slows conduction in cardiac tissue by altering transport of ion across membranes; causes slight prolongation of refractory periods, decreases rate of rise of action potential without affecting its duration; local anesthetic and moderate negative inotropic effects
Absorption
Bioavailability: 85-90%
Peak plasma time: 2-3 hr (PO)
Therapeutic range: 0.2-1 mcg/mL
Toxicity range: >0.7-1 mcg/mL
Distribution
Protein bound: 40-50%
Vd: 5.5-8.7 L/kg
Metabolism
Undergoes extensive biotransformation to 2 major and several minor metabolites; subject to genetic polymorphism; R-enantiomer is metabolized by hepatic CYP2D6
Metabolites: Meta-O-dealkylated flecainide, meta-O-dealkylated lactam of flecainide (inactive)
Elimination
Half-life: 12 to 27hr; t1/2 increased in renal impairment
Dialyzable: Yes (HD)
Total plasma clearance: 10 mL/min/kg
Excretion: Urine (80-90%), which increases with low urine pH; feces (minor)
Administration
Oral Administration
May take with food
