Flecainide

Usage

• Flecainide acetate is prescribed for the treatment of various cardiac arrhythmias. These include:
  • Paroxysmal supraventricular tachycardia (PSVT), including atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT).
  • Paroxysmal atrial fibrillation (AF) and atrial flutter, particularly in patients with disabling symptoms.
  • Life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia (VT), when other treatments are ineffective or not tolerated.
• Pharmacological classification: Class IC antiarrhythmic.
• Mechanism of Action: Flecainide acts by blocking sodium channels in the heart, thereby slowing the conduction of electrical impulses and suppressing abnormal heart rhythms.

Alternate Names

• International/Regional Variations: Flecainide acetate.
• Brand Names: Tambocor.

How It Works

• Pharmacodynamics: Flecainide’s primary effect is on the heart’s electrical conduction system. It slows conduction velocity in all parts of the heart, particularly in the atria, ventricles, and His-Purkinje system. This effect is more pronounced in depolarized tissue. It also prolongs the refractory period, reducing the heart’s excitability and preventing the recurrence of arrhythmias.
• Pharmacokinetics:
  • Absorption: Flecainide is well-absorbed orally, with bioavailability approaching 90%. Food does not significantly affect absorption.
  • Metabolism: It is primarily metabolized in the liver, mainly by CYP2D6, to two major metabolites, which have minimal antiarrhythmic activity.
  • Elimination: Flecainide is predominantly eliminated renally, with a half-life of 12-27 hours in patients with normal renal function. This necessitates dose adjustments in patients with renal impairment.
• Mode of Action: Flecainide binds to open and inactivated sodium channels in cardiac myocytes, blocking the inward flow of sodium ions and slowing the upstroke of the action potential. This reduces conduction velocity and increases the refractory period, thereby suppressing abnormal automaticity and reentry circuits responsible for arrhythmias.
• Receptor Binding/Enzyme Inhibition: Flecainide primarily acts on sodium channels. It is also a weak inhibitor of CYP2D6.
• Elimination Pathways: Primarily renal excretion, with a small amount metabolized by CYP2D6 in the liver.

Dosage

Standard Dosage

Adults:

• PSVT and Paroxysmal AF: Initial dose: 50 mg twice daily. The dose can be increased by 50 mg every 4 days, up to a maximum of 300 mg/day.
• Sustained VT: Initial dose: 100 mg twice daily (initiate in hospital). The dose can be increased by 50 mg every 4 days, up to a maximum of 400 mg/day.

Children (older than 1 month):

• Initial dose: 1-3 mg/kg/day or 50-100 mg/m²/day orally divided into 2-3 doses.
• Usual dose: 3-6 mg/kg/day or 100-150 mg/m²/day divided into 2-3 doses.
• Maximum dose: Up to 8 mg/kg/day or 200 mg/m²/day in uncontrolled patients with subtherapeutic levels. Higher doses may increase the risk of proarrhythmia.
• Pediatric Safety Considerations: Close monitoring is necessary, especially in infants and younger children. Dosage must be adjusted based on age, weight, and therapeutic response.

Special Cases:

• Elderly Patients: The initial dose should not exceed 100 mg daily (or 50 mg twice daily), as the rate of flecainide elimination is reduced. Titrate cautiously and monitor closely. The maximum dose for the elderly is 300 mg/day.
• Patients with Renal Impairment:
  • Severe (CrCl <35 mL/min): 100 mg daily or 50 mg twice daily.
  • Moderate (CrCl >25 mL/min but less than normal): Dose adjustment may be needed. Monitor closely.
• Patients with Hepatic Dysfunction: Use with caution only if benefits outweigh risks. Monitor plasma levels regularly and reduce the dose as necessary. Start with a lower dose (e.g., 100 mg daily) and titrate slowly.
• Patients with Comorbid Conditions: Use cautiously in patients with heart failure or a history of myocardial infarction. Monitor closely for worsening of heart failure symptoms.

Clinical Use Cases

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Flecainide is not typically used for rhythm control during these procedures. However, it can be continued in patients already receiving it for chronic arrhythmia management, with careful monitoring.
• Emergency Situations (e.g., status epilepticus, cardiac arrest):
  • For rapid effect, 1–2 mg/kg IV over 10 minutes, or in divided doses, up to 150 mg.
  • If needed, an infusion can be administered at 1.2–1.5 mg/kg/h during the first hour, and 0.12–0.25 mg/kg/h during subsequent hours.
  • Infuse for no longer than 24 h.

Dosage Adjustments:

• Dose adjustments are based on patient-specific factors like age, renal/hepatic function, coexisting medical conditions, and drug interactions.
• Plasma level monitoring is recommended to optimize therapy and minimize the risk of side effects. The therapeutic plasma range is generally 200-1000 ng/mL.

Side Effects

Common Side Effects:

• Dizziness, lightheadedness, visual disturbances, blurred vision
• Nausea, vomiting, constipation
• Headache, fatigue, tremor
• Palpitations

Rare but Serious Side Effects:

• Worsening of arrhythmias (proarrhythmic effect), including VT or ventricular fibrillation
• New or worsening heart failure
• Bradycardia, heart block
• Sudden cardiac arrest

Long-Term Effects:

• Chronic heart failure exacerbation
• Proarrhythmic effects

Adverse Drug Reactions (ADR):

• Agranulocytosis, thrombocytopenia
• Pulmonary fibrosis
• Hepatic dysfunction

Contraindications

• Second- or third-degree AV block without a pacemaker
• Right bundle branch block with left hemiblock without a pacemaker
• Cardiogenic shock, history of myocardial infarction
• Pre-existing heart failure
• Known Brugada syndrome

Drug Interactions

• Amiodarone: Increases flecainide levels. Reduce flecainide dose by 50% and monitor closely.
• Cimetidine: Increases flecainide levels. Close monitoring and dose reduction may be necessary.
• Digoxin: Flecainide may increase digoxin levels. Monitor digoxin levels.
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): May increase flecainide levels. Dose adjustment may be required.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Breastfeeding: Flecainide is excreted in breast milk. The risks and benefits of breastfeeding while taking flecainide should be carefully considered.

Drug Profile Summary

• Mechanism of Action: Sodium channel blocker.
• Side Effects: Dizziness, visual disturbances, nausea, proarrhythmia, heart failure.
• Contraindications: AV block, heart failure, Brugada syndrome.
• Drug Interactions: Amiodarone, cimetidine, digoxin, CYP2D6 inhibitors.
• Pregnancy & Breastfeeding: Category C; excreted in breast milk.
• Dosage: See detailed dosage guidelines above.
• Monitoring Parameters: ECG, heart rate, blood pressure, plasma flecainide levels, renal and liver function tests.

Popular Combinations

• Flecainide is sometimes used in combination with beta-blockers or other antiarrhythmic drugs, but close monitoring is necessary due to the increased risk of side effects.

Precautions

• General Precautions: Careful patient selection is essential. Thorough cardiac evaluation, including ECG, should be performed before starting flecainide. Monitor for proarrhythmic effects, especially during initiation and dose adjustments. Correct electrolyte imbalances before initiating therapy.

• Specific Populations: As described above for dosing information.

• Lifestyle Considerations: Advise patients to avoid alcohol, as it can potentiate some side effects. Caution patients about driving or operating machinery until the effects of the medication are known.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Flecainide?

A: See detailed dosage guidelines above.

Q2: What are the major side effects of Flecainide?

A: Major side effects include dizziness, visual disturbances, nausea, proarrhythmia, and new or worsening heart failure.

Q3: Who should not take Flecainide?

A: Flecainide is contraindicated in patients with AV block, existing heart failure, Brugada syndrome, history of MI.

Q4: How does Flecainide interact with other medications?

A: Flecainide interacts with amiodarone, cimetidine, digoxin, and CYP2D6 inhibitors. These interactions can lead to increased flecainide levels and an increased risk of side effects.

Q5: Can Flecainide be used during pregnancy or breastfeeding?

A: Flecainide is a Pregnancy Category C drug and should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. It is excreted in breast milk, so the risks and benefits of breastfeeding while on flecainide should be evaluated carefully.

Q6: What are the signs of Flecainide overdose?

A: Signs of overdose include nausea, vomiting, convulsions, hypotension, bradycardia, widening of PR and QT intervals, ventricular tachycardia, AV block, asystole, cardiac and respiratory failure.

Q7: What should be monitored in patients taking Flecainide?

A: ECG, heart rate, blood pressure, plasma flecainide levels, renal function tests, and liver function tests should be monitored.

Q8: How does Flecainide work at the cellular level?

A: Flecainide blocks sodium channels in cardiac myocytes, slowing the upstroke of the action potential and reducing conduction velocity.

Q9: What type of arrhythmias is Flecainide used to treat?

A: Flecainide is used to treat various arrhythmias including PSVT, atrial fibrillation, atrial flutter, and life-threatening ventricular arrhythmias.

Q10: What is the role of therapeutic drug monitoring with Flecainide?

A: Therapeutic drug monitoring helps to ensure that flecainide plasma levels are within the therapeutic range (200-1000 ng/mL), optimizing efficacy and minimizing the risk of side effects.