Flecainide Acetate

Question 1

Antiarrhythmic class

Answer 1

• Class IC

Question 2

Mechanism of action

Answer 2

• Dose-related ↑ in PR, QRS, QT intervals
• Greatest effect on His-Purkinje ventricular
conduction system
• Membrane stabilizer

Question 3

Indications

Answer 3

• In patients without structural heart disease, indicated for the prevention of
— Paroxysmal SVT
— Paroxysmal AF/AFL with disabling symptoms — Life-threatening, documented VA

Question 4

Oral Dosing Strengths

Answer 4

• 50 mg, 100 mg, 150 mg

Question 5

Dosing

Answer 5

• 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

Question 6

Treatment setting

Answer 6

• Should be initiated in-hospital

with rhythm monitoring for sustained VT

Question 7

Monitoring requirements at initiation

Answer 7

• In-hospital rhythm monitoring at initiation for sustained VT

Question 8

Pharmacokinetics

Answer 8

• ~Dose proportional

Question 9

Bioavailability/ absorption

Answer 9

• No presystemic biotransformation
• Food/antacid does not affect absorption • Steady-state plasma levels achieved
within 3–5 days

Question 10

Half-life

Answer 10

• ~20 hours

Question 11

Protein binding

Answer 11

40%

Question 12

Metabolism

Answer 12

• Extensive metabolism; no first-pass effect

* CYP2D6 involved

Question 13

Major active metabolite

Answer 13

1 active urinary metabolite: meta-O-dealkylated flecainide
— Plasma levels of metabolites are low
— One-fifth as active as flecainide

Question 14

Route of elimination

Answer 14

• ~30% renal excretion as unchanged drug

* 5% excreted in feces

Question 15

Overdosage

Answer 15

• 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

Question 16

Contraindications

Answer 16

• Pre-existing 2nd- or 3rd-degree AV block or right BBB with bifascicular block and without a pacemaker
• Cardiogenic shock
• Hypersensitivity to drug

Question 17

Boxed Warning

Answer 17

• 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

Question 18

Warnings(except boxed warning—see above)

Answer 18

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

Question 19

Precautions

Answer 19

• 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

Question 20

Drug interactions

Answer 20

• 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

Question 21

Adverse Reactions

Answer 21

• 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%)