Class IC Antiarrhythmic Drugs

Class IC antiarrhythmic drugs block sodium channels with slow unbinding, strongly slowing conduction in atria, ventricles, His-Purkinje tissue and accessory pathways, with little change in action potential duration. Flecainide and propafenone are used for supraventricular arrhythmia in people with structurally normal hearts. They increase mortality in patients with previous myocardial infarction or structural heart disease.

Members. Flecainide, propafenone. Encainide and moricizine are withdrawn.

Mechanism. Slow dissociation (over 10 seconds) means block persists between beats at normal rates, widening the QRS and prolonging the PR and His-Purkinje intervals even at rest. Flecainide also inhibits the ryanodine receptor, which explains its effect in catecholaminergic polymorphic ventricular tachycardia. Propafenone has weak beta blocking and calcium channel activity.

Evidence of harm. The Cardiac Arrhythmia Suppression Study showed higher mortality with flecainide and encainide after infarction, driven by ischaemia-related proarrhythmia. The finding extends to all structural disease.

Pharmacokinetics. Flecainide has bioavailability about 90%, a half-life of 12 to 27 hours, and clearance split between the kidney and CYP2D6. Propafenone has dose-dependent first pass metabolism by CYP2D6 to an active metabolite, so exposure differs greatly between extensive and poor metabolisers.

• Flecainide: atrial fibrillation, atrial flutter, supraventricular tachycardia, catecholaminergic polymorphic ventricular tachycardia, and foetal tachycardia.
• Propafenone: atrial fibrillation and supraventricular tachycardia; adds beta blockade and can cause bronchospasm.

• Maintenance, normal heart: flecainide 50 to 150 mg twice daily (maximum 300 mg daily), or propafenone 150 to 300 mg three times daily (slow release 225 to 425 mg twice daily), usually with an atrioventricular nodal blocker to prevent 1 to 1 flutter conduction.
• Acute cardioversion of recent-onset atrial fibrillation: flecainide 2 mg/kg intravenously over 10 minutes (maximum 150 mg) or oral 200 to 300 mg, in monitored care.
• Pill-in-the-pocket: flecainide 200 mg (under 70 kg) or 300 mg (70 kg or over), or propafenone 450 mg (under 70 kg) or 600 mg (70 kg or over), after safe supervised first use, for infrequent, well tolerated episodes.
• Catecholaminergic polymorphic ventricular tachycardia: flecainide 100 to 200 mg daily in two divided doses added to a beta blocker such as nadolol.
• Foetal supraventricular tachycardia: transplacental flecainide under specialist care.
• Selection: use only after echocardiography shows normal structure and coronary disease is excluded, and stop if new heart disease appears.

Contraindications. Previous myocardial infarction, coronary disease, heart failure or reduced ejection fraction, left ventricular hypertrophy, valve disease with haemodynamic effect, cardiomyopathy, bifascicular block, sick sinus syndrome, second or third degree block, Brugada syndrome, and cardiogenic shock.

Adverse effects. Proarrhythmia including ventricular tachycardia and atrial flutter with 1 to 1 conduction, QRS widening, negative inotropy, dizziness, blurred or double vision, tremor, headache, nausea, and raised pacing thresholds in paced patients. Propafenone adds a metallic taste and bronchospasm.

Interactions. CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine, terbinafine) raise levels. Digoxin and warfarin exposure rises with propafenone. Beta blockers, verapamil and diltiazem add negative inotropy and conduction block. Amiodarone raises flecainide levels.

Monitoring. Electrocardiogram before starting, after 3 to 5 days and after each dose change, with dose reduction if QRS widens by more than 25% of baseline or reaches 120 ms. Echocardiogram before starting. Flecainide trough level 0.2 to 1.0 micrograms/mL where used.

Referral and escalation. Syncope, new heart failure, wide-complex tachycardia or pronounced QRS widening needs drug withdrawal and urgent care. Flecainide toxicity is treated with sodium bicarbonate 50 to 100 mmol intravenously, supportive care and lipid emulsion in refractory collapse.

Special groups. Renal impairment: flecainide 100 mg daily if creatinine clearance is under 35 mL/min, with level monitoring. Hepatic impairment: reduce doses. Older adults: start low. Pregnancy: flecainide is used in foetal tachycardia. Poor CYP2D6 metabolisers: higher exposure and adverse effects.