Flecainide Acetate Flashcards
Antiarrhythmic class
• Class IC
Mechanism of action
• Dose-related ↑ in PR, QRS, QT intervals
• Greatest effect on His-Purkinje ventricular
conduction system
• Membrane stabilizer
Indications
• In patients without structural heart disease, indicated for the prevention of
— Paroxysmal SVT
— Paroxysmal AF/AFL with disabling symptoms — Life-threatening, documented VA
Oral Dosing Strengths
• 50 mg, 100 mg, 150 mg
Dosing
• Paroxysmal SVT and paroxysmal AF
— 50 mg BID starting dose
— ↑ in 50-mg BID increments every 4 days up to 300 mg/day
• Sustained VT
— 100 mg BID
— ↑ in 50-mg BID increments every 4 days up to 400 mg/day
Adjust dose with renal dysfunction and titrate more slowly with renal or hepatic disease
Treatment setting
• Should be initiated in-hospital
with rhythm monitoring for sustained VT
Monitoring requirements at initiation
• In-hospital rhythm monitoring at initiation for sustained VT
Pharmacokinetics
• ~Dose proportional
Bioavailability/ absorption
• No presystemic biotransformation
• Food/antacid does not affect absorption • Steady-state plasma levels achieved
within 3–5 days
Half-life
• ~20 hours
Protein binding
40%
Metabolism
- Extensive metabolism; no first-pass effect
* CYP2D6 involved
Major active metabolite
1 active urinary metabolite: meta-O-dealkylated flecainide
— Plasma levels of metabolites are low
— One-fifth as active as flecainide
Route of elimination
- ~30% renal excretion as unchanged drug
* 5% excreted in feces
Overdosage
• No antidote
• Effects include nausea, vomiting,
convulsions, hypotension, bradycardia, syncope; ↑ QRS complex, QT interval, PR interval; VT, AV nodal block, asystole, BBB, cardiac failure, cardiac arrest
• Treatment supportive: remove drug from GI tract, administer inotropic agents, cardiac stimulants, respiratory ventilator, circulatory assistance, transvenous pacing
• Fatal cases have occurred
Contraindications
- Pre-existing 2nd- or 3rd-degree AV block or right BBB with bifascicular block and without a pacemaker
- Cardiogenic shock
- Hypersensitivity to drug
Boxed Warning
- Mortality: Excessive mortality or nonfatal cardiac arrest in patients with non–life- threatening VA who had an MI >6 days and <2 years prior; CAST showed 5.1% mortality rate for Tambocor and 2.3% for controls
- Ventricular proarrhythmic effects: 0.4% in paroxysmal AF and 10.5% in chronic AF
- Not recommended in chronic AF
- Can cause 1:1 AV conduction
Warnings(except boxed warning—see above)
Bolded Warnings
• Can cause or worsen SVA, VA, or CHF
Warnings • Slows cardiac conduction • May cause SSS • ↑ pacemaker thresholds • Electrolyte disturbances (hypokalemia or hyperkalemia) may alter effects • Pediatric: can cause proarrhythmic effects, cardiac arrest, death
Precautions
• Pregnancy Category C: embryotoxic effects in animals
• Nursing mothers: drug is excreted through
breast milk
• Pediatric use: safety and efficacy have not
been determined
• Hepatic impairment: use with caution; plasma monitoring is required
Drug interactions
• Drugs that may affect flecainide exposure or have pharmacodynamic interaction:
— b-blockers (propranolol)
— Enzyme inducers (phenytoin, phenobarbital,
carbamazepine)
— Cimetidine
— Amiodarone
— CYP2D6 inhibitors (quinidine)
— Little experience with disopyramide, verapamil, nifedipine, diltiazem
• Drugs that may be affected by flecainide: — Digoxin
— Propranolol
No apparent interaction with diuretics; interaction with highly protein-bound anticoagulants not expected
Adverse Reactions
• In post-MI patients with PVC, death was 5.1% Tambocor (n=315) vs 2.3% placebo (n=309)
• New or worsened arrhythmias (proarrhythmia) in 1% of 108 paroxysmal SVT patients and 7% of 117 paroxysmal AF patients
• New or worsened CHF, 2nd- or 3rd-degree AV block, sinus bradycardia, sinus arrest may occur
• Common noncardiac arrhythmias are similar for
AF and VA patients
• Of 429 patients with VA, most common AEs:
— Dizziness (18.9%)
— Visual disturbance (15.9%) — Dyspnea (10.3%)
— Headache (9.6%)
— Nausea (8.9%)
— Fatigue (7.7%)
— Palpitations (6.1%)
— Chest pain (5.4%)
— Asthenia (4.9%)
— Tremor (4.7%)
— Constipation (4.4%)
— Edema (3.5%)
— Abdominal pain (3.3%)
