Flecainide

Flecainide is a class IC antiarrhythmic that blocks sodium channels strongly and slowly. It prevents paroxysmal atrial fibrillation and supraventricular tachycardia in patients with a structurally normal heart, and it can end a recent episode of atrial fibrillation as a single "pill in the pocket" dose. It is dangerous in coronary disease, after myocardial infarction, and in heart failure, where it raises mortality. It is available in some East African tertiary centres but is seldom stocked in district pharmacies.

Classification. Class IC antiarrhythmic (sodium channel blocker).

Mechanism. Blocks the fast sodium channel with slow recovery kinetics, which slows conduction in the atria, ventricles and accessory conduction tracts, and lengthens the QRS duration. It also blocks ryanodine receptor calcium release, which is why it is used in catecholaminergic polymorphic ventricular tachycardia.

Pharmacodynamics. Oral onset within 1 to 3 hours, peak at about 3 hours. Prolongs PR and QRS intervals in a rate dependent manner (use dependence), so the effect increases with faster rates and exercise. Little effect on the QT interval.

Pharmacokinetics. Oral bioavailability about 90%. Half life 12 to 27 hours (longer in kidney or heart failure). Metabolised by CYP2D6 in the liver; about 30% excreted unchanged in urine. Therapeutic plasma level 0.2 to 1.0 mg/L.

Paroxysmal atrial fibrillation or supraventricular tachycardia, prevention, adult.

• Start 50 mg twice daily.

• Increase every 3 to 4 days to 100 mg twice daily, then 150 mg twice daily as needed.

• Usual maintenance 100 to 150 mg twice daily; maximum 300 mg daily.

Recent onset atrial fibrillation, single dose ("pill in the pocket"), adult. 200 mg orally for a body weight under 70 kg, or 300 mg for 70 kg and over, taken once in a single episode; do not repeat within 24 hours. Give the first dose under observation. Only for patients who have tolerated it before, with a normal heart, and who take an atrioventricular nodal blocking drug (a beta blocker) to prevent a rapid flutter response.

Cardioversion of recent onset atrial fibrillation, adult (IV, monitored). 2 mg/kg (maximum 150 mg) by IV infusion over 10 to 30 minutes; do not repeat.

Ventricular arrhythmias (specialist), adult. 100 mg twice daily initially; increase to a maximum of 400 mg daily with monitoring.

Children (specialist). 2 to 4 mg/kg daily in 2 or 3 divided doses (up to 8 mg/kg daily in a neonate under close observation); maximum 200 mg a dose. Use under specialist care only.

Contraindications. Structural heart disease (coronary disease, previous myocardial infarction, left ventricular hypertrophy, cardiomyopathy); heart failure or left ventricular ejection fraction under 40%; Brugada syndrome; sick sinus syndrome, atrioventricular or bundle branch block without a pacemaker; cardiogenic shock; long standing (persistent) atrial fibrillation; haemodynamically significant valve disease; hypersensitivity.

Warnings. Proarrhythmia (ventricular tachycardia, atrial flutter with 1 to 1 conduction); negative inotropy; rising pacing thresholds in pacemaker patients; worsening of conduction block; hypokalaemia and hyperkalaemia both increase risk. Large studies after myocardial infarction showed higher death rates with class IC drugs.

Adverse effects. Dizziness, blurred vision, headache, nausea, tremor, dyspnoea, palpitations, proarrhythmia, atrioventricular block, heart failure.

Interactions. Amiodarone: raises flecainide levels (halve the dose). Digoxin: raised levels. Beta blockers and calcium channel blockers (verapamil, diltiazem): bradycardia, negative inotropy. CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine, ritonavir): levels rise. Cimetidine: levels rise. QT prolonging drugs: torsades (especially antimalarials). Enzyme inducers (rifampicin, carbamazepine): lower levels.

Special groups.

• Pregnancy: used for foetal supraventricular tachycardia under specialist care; monitor foetus.

• Breastfeeding: excreted in milk; avoid or monitor infant closely.

• Patients of African ancestry: no dose change; check for hypertensive heart disease before use.

• Older adults: start 50 mg twice daily; accumulation is common.

• Kidney impairment: creatinine clearance under 35 mL/min: start 50 mg once or twice daily, and monitor plasma levels; maximum 100 mg twice daily.

• Liver impairment: use lower doses; monitor levels.

Formulations. Tablets 50 and 100 mg; modified release capsules 100, 150, 200 mg; injection 10 mg/mL.

Administration. Oral twice daily with or without food. IV: dilute in 5% glucose only (precipitation with chloride); infuse by pump with continuous ECG.

Baseline. ECG (PR, QRS), echocardiogram to exclude structural disease, potassium, magnesium, creatinine, liver enzymes, stress test if coronary disease is possible.

Monitoring. ECG after 2 to 3 days of each dose change and at least yearly; QRS widening of more than 25% from baseline means stop or reduce the dose. Plasma level in kidney or liver disease. Potassium and magnesium. Heart failure symptoms.

Stopping. No taper needed, but arrhythmias can recur.

Common prescribing errors. Prescribing in coronary disease or heart failure without imaging; omitting an atrioventricular nodal blocker in atrial flutter; failing to halve the dose with amiodarone; repeating the pill in the pocket dose; mixing with sodium chloride infusion.