Flecainide: English spelling of the class 1c antiarrhythmic flecainid

Flecainide is the English spelling of the substance flecainid. International literature and the USA consistently use flecainide; in Germany flecainid is common. Pharmacologically the same Vaughan Williams class 1c antiarrhythmic is meant, used mainly for supraventricular tachycardia and paroxysmal atrial fibrillation.

Flecainide was approved in the USA in 1985. The CAST trial (Cardiac Arrhythmia Suppression Trial) in post-infarction patients showed paradoxically increased mortality under class 1 antiarrhythmics, leading to a tightly defined indication. In patients with structurally healthy hearts, flecainide remains one of the most effective options for cardioversion and rhythm maintenance.

Mechanism of action

Flecainide blocks voltage-gated Nav1.5 sodium channels in the activated and partly inactivated state. Characteristic for class 1c is strong inhibition of phase 0 of the action potential with marked slowing of conduction in atrium, AV node and ventricle. Repolarisation duration is barely affected.

Clinically this slows conduction with widening of the QRS complex on ECG. This makes flecainide particularly effective for cardioversion and prevention of atrial fibrillation and supraventricular tachycardia.

In patients with structural heart disease, however, the slowed conduction can promote ventricular tachycardia, which is why flecainide is contraindicated there.

Indications

• Paroxysmal atrial fibrillation in structurally healthy hearts: conversion to sinus rhythm and rhythm maintenance
• Pill-in-the-pocket concept: oral on-demand therapy for self-limited atrial fibrillation episodes
• AV nodal reentry tachycardia (AVNRT): when beta-blockers and calcium antagonists fail
• WPW syndrome with reentry tachycardia: reserve therapy
• Ventricular tachyarrhythmias in structurally healthy hearts: rare, in specialised centres
• Catecholaminergic polymorphic ventricular tachycardia (CPVT): off-label, effective when beta-blockers are insufficient

Contraindicated in structural heart disease, post-infarction state, severe heart failure and existing conduction disorders.

Dosing and administration

Maintenance therapy orally: 50 to 100 mg twice daily, with stepwise titration. Maximum dose 300 to 400 mg per day.

Pill-in-the-pocket: 200 to 300 mg as a single dose at onset of an atrial fibrillation episode, often combined with an AV-blocking substance (beta-blocker or verapamil) to avoid 1:1 conduction in atrial flutter.

Acute conversion intravenously: 1.5 to 2 mg per kg body weight over 10 to 20 minutes under ECG monitoring in a clinical setting.

Oral intake is independent of meals. Therapeutic drug monitoring (range 200 to 1,000 ng/ml) is sensible in at-risk patients.

Checks: ECG before therapy, after titration and every 3 to 6 months. QRS prolongation by more than 25 % calls for dose reduction.

Side effects

Common: dizziness, visual disturbance (blurred vision, double vision), nausea, headache, asthenia, tremor, dyspnoea.

Uncommon: palpitations, bradycardia, AV block, worsening heart failure, depressive mood, sleep disturbance, tinnitus, rash.

Rare and very rare: proarrhythmia (worsening of existing or triggering of new arrhythmias), especially ventricular tachycardia, Stevens Johnson syndrome, pneumonitis, hepatitis, thrombocytopenia, leukopenia, lupus-like reaction.

Important safety points:

• Proarrhythmic effects are the most dangerous complication, especially with structurally diseased hearts
• Echocardiography before therapy to assess LV function
• ECG checks at titration and follow-up
• The pill-in-the-pocket concept requires prior supervised intake in a clinical setting to test individual tolerability
• Caution with electrolyte disturbances, especially hypokalaemia

Interactions

• Other antiarrhythmics (amiodarone, sotalol, class 1a substances): additive effect, risk of proarrhythmia, mostly avoid combination
• Beta-blockers and calcium channel blockers: additive negative inotropic and chronotropic effect, often clinically intended in pill-in-the-pocket strategy, but controlled
• CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion, quinidine): level increase, caution
• Digoxin: rise of digoxin levels by about 15 %
• Diuretics: hypokalaemia increases toxicity
• Cimetidine: moderate level increase
• Urine alkalinisation (acetazolamide, sodium bicarbonate): reduced renal excretion of flecainide

Special considerations

Pregnancy: flecainide is one of the few antiarrhythmics with good data in pregnancy, especially for fetal tachycardia. With maternal indications, individual judgement.

Breastfeeding: passes into milk, usually clinically tolerable.

Contraindications: recent myocardial infarction, severe heart failure, marked conduction disorders without pacemaker, severe renal impairment.

Renal impairment: dose reduction required. With GFR below 35 ml/min usually half the dose is recommended.

Liver disease: prolonged half-life, caution.

Pill-in-the-pocket concept: requirements: structurally healthy heart, prior supervised intake in hospital to assess tolerability, sufficient self-perception of atrial fibrillation episodes, joint agreement on indication criteria (episode duration, frequency). Prior AV-blocking co-medication reduces the risk of fast conduction in atrial flutter.

Patient communication: clear instructions on when the drug is used, when an emergency exists and which symptoms require medical review.

Related substances

• Flecainid, German spelling of the same substance
• Propafenone, another class 1c antiarrhythmic
• Quinidine, class 1a antiarrhythmic
• Mexiletine, class 1b antiarrhythmic
• Dabigatran etexilate as anticoagulation in atrial fibrillation

Frequently asked questions

Sources

• EMA European Medicines Agency
• BfArM Federal Institute for Drugs and Medical Devices
• AWMF atrial fibrillation guideline
• Gelbe Liste flecainid monograph