Why this drug is interesting
Flecainide is the drug behind one of the most consequential trials in cardiology. The Cardiac Arrhythmia Suppression Trial tested the entirely reasonable hypothesis that suppressing ventricular ectopics after myocardial infarction would reduce sudden death. It did the opposite: mortality increased in the treatment arm. The SmPC still carries the finding in plain terms — flecainide "has been shown to increase mortality risk of post-myocardial infarction patients with asymptomatic ventricular arrhythmia".1
CAST is the origin of the modern distinction between a surrogate endpoint and an outcome that matters, and it is why flecainide's contraindication list is the most important part of this monograph. In the right patient it is genuinely excellent; the skill is entirely in deciding who the right patient is.
Pharmacology
Mechanism
Flecainide is a class Ic agent: a potent sodium channel blocker with slow dissociation kinetics. It markedly depresses phase 0 upstroke velocity and slows conduction through atrial and ventricular myocardium, the His-Purkinje system and accessory pathways, with comparatively little effect on action potential duration.
Slow dissociation is the key property and the source of the danger. Because the block deepens as heart rate rises — use dependence — conduction slows most at exactly the moments a diseased heart can least tolerate it: tachycardia, ischaemia, and the border zones of infarct scar. In a heart with no scar, this produces effective rhythm control. In a heart with scar, it produces re-entry.
Kinetics
- Half-life
- Approximately 12–27 hours; longer in the elderly and in cardiac or renal impairment
- Metabolism
- Hepatic, principally via CYP2D6 — poor metabolisers reach higher concentrations
- Excretion
- Roughly 30% renal as unchanged drug
- Oral bioavailability
- High — around 90%, which is what makes pill-in-the-pocket workable
Indications and dosing
The licensed indications are:1
- AV nodal reciprocating tachycardia; arrhythmias associated with Wolff-Parkinson-White syndrome
- Severe symptomatic and life-threatening paroxysmal ventricular arrhythmia
- Paroxysmal atrial arrhythmias — atrial fibrillation, atrial flutter and atrial tachycardia — explicitly excluding patients with structural heart disease and impaired left ventricular function
Chemical cardioversion of recent-onset AF
The commonest emergency use. In a patient with recent-onset atrial fibrillation, a structurally normal heart and appropriate anticoagulation/duration considerations, intravenous flecainide restores sinus rhythm in a high proportion of cases, often within an hour.
The standard UK intravenous regimen is 2 mg/kg to a maximum of 150 mg, given over 10–30 minutes. Intravenous flecainide must be initiated in hospital, and the SmPC requires continuous ECG monitoring in all patients receiving bolus injection.1
Pill in the pocket
Selected patients with infrequent, symptomatic, self-terminating paroxysmal AF and no structural heart disease may be given a single oral loading dose to self-administer at home. The first dose must be given under supervision in hospital to confirm it is tolerated. This is a cardiology-initiated strategy, not something to start from the ED.
Diagnostic use
Flecainide — more usually ajmaline in UK practice — is used deliberately as a provocation test to unmask Brugada syndrome by exposing the type 1 ECG pattern. That this is a recognised diagnostic use is the clearest possible statement of why it is contraindicated in known Brugada.
Contraindications — the critical section
In practice, before giving flecainide
- Is there any history of ischaemic heart disease, infarction, heart failure or cardiomyopathy? Any yes is a stop.
- Is left ventricular function known and normal? An unknown LV in an older patient with risk factors is not the same as a normal one.
- Does the ECG show conduction disease, or a Brugada-type pattern?
- How long has the AF been present, and what is the anticoagulation and stroke-risk position?
- Is this actually atrial flutter? See below.
Adverse effects and interactions
Proarrhythmia
The defining risk. The SmPC states that flecainide, like other antiarrhythmics, may cause the appearance of a more severe type of arrhythmia, increase the frequency of an existing arrhythmia, or increase the severity of symptoms.1 The mechanism is slowed conduction creating the substrate for re-entry, which is why it is most dangerous where conduction is already abnormal.
Progressive QRS widening on the monitor is the warning sign. A widening QRS during or after administration should prompt immediate reassessment rather than reassurance.
Other adverse effects
- Visual disturbance — blurred vision and diplopia are characteristic and dose-related
- Dizziness, light-headedness, tremor, paraesthesia
- Nausea, vomiting
- Negative inotropy — precipitation or worsening of heart failure
- Bradycardia, sinus arrest, AV block
- Rarely, hepatic dysfunction and blood dyscrasias
Interactions
- CYP2D6 inhibitors — fluoxetine, paroxetine, bupropion, quinidine, terbinafine — raise flecainide concentrations
- Amiodarone raises flecainide levels substantially; the amiodarone SmPC advises reducing the flecainide dose by 50% and monitoring closely
- Other negative inotropes and AV nodal blockers — additive effects on conduction and contractility
- Digoxin concentrations may rise
Critical appraisal
- CAST remains one of the most important negative trials in medicine, and its lesson generalises far beyond flecainide: suppressing an abnormality visible on a monitor is not the same as improving survival. Any teaching of this drug that omits CAST has missed the point of it.
- The efficacy evidence for cardioversion of recent-onset AF is good, with conversion rates that compare favourably with amiodarone and with a faster onset. Within its licensed population, flecainide works.
- The safety of the strategy depends on a judgement — 'structurally normal heart' — that the ED is often poorly placed to make. A patient with no diagnosed cardiac history is not the same as a patient with a documented normal echocardiogram, and this uncertainty is the practical reason many departments restrict flecainide to cardiology-directed use.
- Rate control versus rhythm control is a wider debate that this monograph does not settle. Whether a given ED patient with recent-onset AF needs chemical cardioversion at all — as opposed to rate control and outpatient follow-up — is a genuine clinical question and depends on symptoms, duration, stroke risk and local pathways.
- The 1:1 flutter hazard is under-taught relative to how badly it can go, and is a good argument for electrical cardioversion in flutter.
References
- 1Flecainide Acetate 100 mg tablets — Summary of Product Characteristics. electronic Medicines Compendium. Sections 4.1, 4.3, 4.4. Verified 20 Aug 2026. This is the oral SmPC and carries no intravenous posology — consult the SmPC for the injection preparation stocked locally.
- 2Flecainide acetate — dosing and safety monograph, including intravenous regimens. BNF, NICE. bnf.nice.org.uk
- 3Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo — the Cardiac Arrhythmia Suppression Trial (CAST). N Engl J Med 1991;324(12):781–88.
- 4Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation. Eur Heart J 2021;42(5):373–498.
- 5NICE NG196. Atrial fibrillation: diagnosis and management. National Institute for Health and Care Excellence.
- 6TOXBASE — flecainide and sodium channel blocker poisoning. National Poisons Information Service. toxbase.org (NHS login required.)