Flecainide acetate

What it is

Flecainide acetate is a prescription tablet that slows the electrical signal travelling through heart muscle. It is a local-anaesthetic-type sodium channel blocker in the Class IC group, acting most strongly on the His-Purkinje conduction system. It is almost completely absorbed, has a half-life of roughly 12 to 27 hours, and is cleared partly by the liver enzyme CYP2D6 and partly unchanged by the kidneys.

What the research says

For rhythm control it works. A Cochrane review of 59 randomised trials found flecainide cut atrial fibrillation recurrence by about a third (RR 0.65), and a long-term study found most people with paroxysmal supraventricular tachycardia became attack-free. What it does not do is improve survival. In the CAST trial, patients given flecainide after a heart attack died more often than those on placebo (5.1% versus 2.3% death or non-fatal cardiac arrest), and that result is the drug’s boxed warning. The same Cochrane review found a near fivefold increase in proarrhythmia. Its place is therefore in people without structural heart disease whose arrhythmia is symptomatic.

Evidence grade: Disputed.

How it works

Drug class: Class IC antiarrhythmic (cardiac sodium channel blocker, membrane-stabilising agent)

Flecainide blocks the sodium channels that start each heartbeat’s electrical impulse, so the signal travels more slowly through the heart. That slowing can stop an abnormal circuit from sustaining itself, which is how it suppresses atrial fibrillation and supraventricular tachycardia. The same slowing can create new abnormal circuits, which is why it can cause the arrhythmias it is meant to prevent, and it also weakens heart muscle contraction. (Source 1)

Boxed warning

Flecainide acetate was included in the National Heart Lung and Blood Institute’s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than six days but less than two years previously. An excessive mortality or non-fatal cardiac arrest rate was seen in patients treated with flecainide acetate compared with that seen in patients assigned to a carefully matched placebo-treated group. This rate was 16/315 (5.1%) for flecainide acetate and 7/309 (2.3%) for the matched placebo. The average duration of treatment with flecainide acetate in this study was ten months.

(Source 2)

What it is used for

• A Cochrane review of 59 randomised trials found flecainide reduced atrial fibrillation recurrence (RR 0.65, 95% CI 0.55 to 0.77) with moderate-to-high certainty, but found no evidence of benefit on any other clinical outcome and marked increases in proarrhythmia. Evidence: limited. (Source 3)
• In a long-term extension of placebo-controlled trials, the proportion of patients free of supraventricular tachycardia attacks rose from 24% on placebo baseline to 82% on flecainide (p = 0.013, n = 17). The sample is very small and the long-term phase was open-label. Evidence: limited. (Source 4)
• The label restricts this to life-threatening arrhythmias and states plainly there is no controlled-trial evidence that flecainide improves survival or reduces sudden death. In sustained ventricular tachycardia 13% of 198 patients had new or worsened ventricular arrhythmia. Evidence: disputed. (Source 5)
• The CAST trial tested exactly this and found excess death. Flecainide is contraindicated in this setting; the label states it should not be used after recent myocardial infarction. Evidence: not-supported. (Source 6)
• In 210 pre-selected patients with little or no heart disease, out-of-hospital self-treatment ended 94% of 569 treated episodes, and 12 of the 165 patients who had recurrences (7%) reported adverse effects. This was a single-arm open-label study with no control group, not a randomised comparison. Evidence: limited. (Source 7)
• A single-blind placebo-controlled crossover trial in 13 completers found exercise ventricular arrhythmia suppressed completely in 11 of 13 (85%), and a 247-patient case cross-over analysis found fewer arrhythmic events during the period on flecainide than during the same patients’ earlier period on a beta-blocker alone (incidence rate ratio 0.55, 95% CI 0.38 to 0.83). Evidence: limited. (Source 8)

Interactions

• Amiodarone (pharmacokinetic study): Adding amiodarone can double or more than double flecainide blood levels, and flecainide harms rise with level, so the label directs that the flecainide dose be reduced by half. (The label’s own text runs "amiodaroneis" together, a missing space in the published document.) (Source 9)
• Digoxin (pharmacokinetic study): Flecainide raised digoxin blood levels by 13% to 19% in healthy volunteers. The boxed warning separately notes digoxin or a beta-blocker may reduce the risk of a dangerously fast ventricular response in atrial flutter. (Source 9)
• Propranolol and other beta-blockers (pharmacokinetic study): Flecainide and propranolol each raised the other’s blood level by 20% to 30%, and their weakening effect on heart muscle contraction added together in a formal interaction study. (Source 9)
• Quinidine and other CYP2D6 inhibitors (pharmacokinetic study): Flecainide is broken down by the liver enzyme CYP2D6, so drugs that block that enzyme can push its blood level up, especially in people who are fast metabolisers. (Source 9)
• Cimetidine (pharmacokinetic study): A week of cimetidine raised flecainide blood levels by about 30% in healthy subjects. (Source 9)
• Milk (in infants) (label): Milk reduces how much flecainide an infant absorbs, so taking milk out of an infant’s diet can make the same dose act more strongly. The label asks for a dose reduction in that situation. This is a documented infant-specific effect, not an adult one. (Source 10)
• A strict vegetarian diet, and anything else that makes urine strongly alkaline (pharmacokinetic study): Flecainide leaves the body much more slowly when urine pH reaches 8 or above, which the label says can happen with a strict vegetarian diet or renal tubular acidosis. Slower clearance means higher blood levels on an unchanged dose. (Source 11)
• Ordinary food and antacids (label): A documented absence of interaction: the label states food and antacid do not change how much flecainide is absorbed in adults. (Source 10)
• Phenytoin, phenobarbital and carbamazepine (pharmacokinetic study): These enzyme-inducing drugs sped up flecainide elimination by about 30% in limited data, which would lower its blood level. (Source 9)
• Disopyramide and verapamil (label): The label says these should not be given with flecainide unless a doctor judges the benefit worth the risk, because all of them weaken the force of the heart’s contraction and the combination has barely been studied. It says the same about nifedipine and diltiazem on the grounds of too little experience. (Source 9)

Stopping it

• We found no trial of tapering or stopping flecainide, and the label gives no stopping schedule. What the label does say about timing is that dose increases are spaced no closer than four days apart, because the drug has a long half-life and steady levels in the blood may not be reached for 3 to 5 days. (Source 12)
• On the label's own figures the risky phase is starting, not stopping: in people treated for sustained ventricular tachycardia, 80% (51 of 64) of proarrhythmic events happened within 14 days of starting therapy. (Source 13)
• People do stop it because of side effects. In the Cochrane review every antiarrhythmic increased withdrawals due to adverse effects compared with placebo or no treatment, and the flecainide estimate was extremely imprecise. (Source 14)
• Stopping does not make the arrhythmia go away. The Cochrane review found that even on treatment atrial fibrillation came back in 43% to 67% of people, so the underlying rhythm problem is being suppressed rather than cured. (Source 3)

What goes wrong

In patients with asymptomatic ventricular ectopy after a heart attack, flecainide caused more deaths and cardiac arrests than placebo. (Source 6)

• Randomized trial, High certainty.
• Size: 641 patients randomised to flecainide or its placebo (323 active, 318 placebo) within a 1,498-patient trial.
• Who: patients with asymptomatic non-life-threatening ventricular ectopy 6 days to 2 years after myocardial infarction.
• How long: mean follow-up 10 months.
• Result: 89 deaths overall; 59 arrhythmic deaths, 43 on active drug vs 16 on placebo (P = 0.0004) and 22 non-arrhythmic cardiac deaths, 17 vs 5 (P = 0.01) - these counts pool the encainide and flecainide arms. The flecainide-specific rate, from the boxed warning, is 16/315 (5.1%) vs 7/309 (2.3%)
• Funding: National Heart Lung and Blood Institute (public funding, per the label text)

Limit of this finding: The death counts quoted here (43 versus 16) cover both drugs the trial tested, encainide and flecainide together. The flecainide-only figures, 5.1% against 2.3%, come from the drug label, not from this abstract.

After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo).

The boxed warning records the absolute excess: 5.1% died or had a cardiac arrest on flecainide against 2.3% on matched placebo. (Source 2)

• Official position, High certainty.
• Size: 315 flecainide vs 309 matched placebo.
• Who: post-myocardial-infarction patients with asymptomatic non-life-threatening ventricular arrhythmias.
• How long: average treatment duration ten months.
• Result: 16/315 (5.1%) flecainide vs 7/309 (2.3%) placebo for death or non-fatal cardiac arrest, an absolute excess of 2.8 percentage points.
• Funding: not applicable (FDA-approved labelling quoting a publicly funded trial)

This rate was 16/315 (5.1%) for flecainide acetate and 7/309 (2.3%) for the matched placebo. The average duration of treatment with flecainide acetate in this study was ten months.

The same Cochrane review found flecainide raised proarrhythmia nearly fivefold and had by far the widest confidence interval for withdrawals due to adverse effects. (Source 14)

• Systematic review, Moderate certainty.
• Size: 59 RCTs, 20,981 participants.
• Who: adults maintained in sinus rhythm after cardioversion of atrial fibrillation.
• How long: one year or nearest time point.
• Result: proarrhythmia RR 4.80 (95% CI 1.30 to 17.77); withdrawals due to adverse effects RR 15.41 (95% CI 0.91 to 260.19), certainty rated low for this outcome.
• Funding: Cochrane review; funding not stated in the abstract.

Limit of this finding: The review writes that all the drugs "increased withdrawals due to adverse effects", but the flecainide figure it gives, RR 15.41 with a 95% confidence interval from 0.91 to 260.19, includes no effect at all and is too imprecise to support any number. A range that wide usually means very few events were available. The proarrhythmia figure for flecainide, 4.80 (1.30 to 17.77), does exclude no effect.

flecainide: RR 15.41, 95% CI 0.91 to 260.19; metoprolol: RR 3.47, 95% CI 1.48 to 8.15; amiodarone: RR 6.70, 95% CI 1.91 to 23.45; dofetilide: RR 1.77, 95% CI 0.75 to 4.18; dronedarone: RR 1.58, 95% CI 1.34 to 1.85; sotalol: RR 1.95, 95% CI 1.23 to 3.11). Certainty of the evidence for this outcome was low for disopyramide, amiodarone, dofetilide and flecainide

The label gives arrhythmia-worsening rates by population: 1% in supraventricular tachycardia, 7% in paroxysmal atrial fibrillation, 7% in ventricular arrhythmia, and 13% in sustained ventricular tachycardia. (Source 13)

• Official position, Certainty not rated.
• Size: 108 PSVT, 117 PAF, 1,330 PVC/VT, 198 sustained VT, 1,046 for heart failure outcome.
• Who: patients in the flecainide clinical trial programme.
• How long: up to 22 months in the multicentre study; 80% of proarrhythmic events in sustained VT occurred within 14 days of starting.
• Result: new or worsened arrhythmia 1% of 108 PSVT, 7% of 117 PAF, 7% of 1,330 PVC/non-sustained/sustained VT, 13% of 198 sustained VT; new or worsened heart failure 6.3% of 1,046, 9.1% of 297 with sustained VT, 0.4% of 225 with supraventricular arrhythmias; second-degree AV block 0.5%, third-degree 0.4%, sinus bradycardia/pause/arrest about 1.2%.
• Funding: not applicable (FDA-approved labelling)

Adverse effects reported for flecainide acetate, described in detail in the WARNINGSsection, were new or worsened arrhythmias which occurred in 1% of 108 patients with PSVT and in 7% of 117 patients with PAF; and new or exacerbated ventricular arrhythmias which occurred in 7% of 1,330 patients with PVCs, non-sustained or sustainedVT. In patients treated with flecainide acetate for sustained VT, 80% (51/64) of proarrhythmic events occurred within 14 days of the onset of therapy.

The label’s 300 and 400 mg daily maxima are adult figures: it sets a separate, much lower ceiling for children (200 mg per square metre of body surface area per day, which it says must not be exceeded) and a lower starting dose in severe kidney impairment. (Source 15)

• Official position, Certainty not rated.
• Size: not stated.
• Who: children, and adults with severe renal impairment (creatinine clearance 35 mL/min/1.73 m2 or less)
• How long: not stated.
• Result: children: maximum recommended dose 200 mg/M2 per day, "This dose should not be exceeded"; severe renal impairment: initial dosage 100 mg once daily (or 50 mg twice daily) with frequent plasma level monitoring.
• Funding: not stated.

Under six months of age, the initial starting dose of Flecainide Acetate Tablets, USP in children is approximately 50 mg/M 2body surface area daily, divided into two or three equally spaced doses. Over six months of age, the initial starting dose maybe increased to 100 mg/M 2per day. The maximum recommended dose is 200 mg/M 2per day. This dose should not be exceeded.

What the evidence supports

Flecainide reduced recurrence of atrial fibrillation after cardioversion, but recurrence still happened in most treated people. (Source 3)

• Systematic review, Moderate certainty.
• Size: 59 RCTs, 20,981 participants across nine drugs.
• Who: adults in sinus rhythm after atrial fibrillation was cardioverted.
• How long: results calculated at one year or nearest time point; mean follow-up 10.2 months.
• Result: flecainide RR for recurrence 0.65 (95% CI 0.55 to 0.77); across all antiarrhythmics atrial fibrillation still recurred in 43% to 67% of treated people.
• Funding: Cochrane review; funding not stated in the abstract.

Limit of this finding: In this passage the review says every drug it analysed "reduced recurrence", but two of the figures it lists cross 1 (metoprolol 0.83, 0.68 to 1.02; disopyramide 0.77, 0.59 to 1.01), meaning no effect cannot be ruled out for those two. The flecainide result quoted here, 0.65 (0.55 to 0.77), does not cross 1. Do not read the sentence as showing every listed drug worked.

flecainide: RR 0.65, 95% CI 0.55 to 0.77; metoprolol: RR 0.83 95% CI 0.68 to 1.02; amiodarone: RR 0.52, 95% CI 0.46 to 0.58; dofetilide: RR 0.72, 95% CI 0.61 to 0.85; dronedarone: RR 0.85, 95% CI 0.80 to 0.91; sotalol: RR 0.83, 95% CI 0.80 to 0.87). Despite this reduction, atrial fibrillation still recurred in 43% to 67% of people treated with antiarrhythmics.

In an open-label long-term extension, far more patients were free of attacks on flecainide than during their own earlier placebo-baseline monitoring. (Source 4)

• Case series, Very low certainty.
• Size: 49 patients who had been in short-term double-blind placebo-controlled studies and then took open-label flecainide for 6 months or more.
• Who: patients with paroxysmal supraventricular tachycardia (n = 17) or paroxysmal atrial fibrillation (n = 25)
• How long: mean 17 months of therapy, with 4- or 8-week transtelephonic monitoring windows.
• Result: free of attacks rose from 24% to 82% for supraventricular tachycardia (p = 0.013, n = 17) and from 12% to 68% for atrial fibrillation (p < 0.001, n = 25), each patient compared with their own earlier placebo-baseline monitoring period rather than with a concurrent control group.
• Funding: not stated; conducted by the Flecainide Supraventricular Tachycardia Study Group.

Limit of this finding: There was no control group in this phase. Everyone knew they were taking the drug, and each patient was compared with their own earlier monitoring period, so improvement over time, changes in how carefully attacks were recorded, and the natural ups and downs of the arrhythmia are not ruled out. The groups are also tiny (17 and 25 people). The published abstract is marked "(ABSTRACT TRUNCATED AT 250 WORDS)", so anything beyond this needs the full paper.

Compared with placebo-baseline results, the number of patients free of arrhythmic attacks increased significantly for both patients with SVT (from 24% to 82%, p = 0.013, n = 17) and patients with AF (from 12% to 68%, p < 0.001, n = 25).

Self-administered single-dose flecainide or propafenone ended most recent-onset atrial fibrillation episodes in a pre-selected low-risk group, in a study with no control arm. (Source 7)

• Case series, Low certainty.
• Size: 268 screened, 58 (22%) excluded for treatment failure or side effects, 210 followed.
• Who: patients with mild heart disease or none, haemodynamically well tolerated recent-onset atrial fibrillation; mean age 59 +/- 11.
• How long: mean follow-up 15 +/- 5 months.
• Result: 534 of 569 treated episodes resolved (94%); symptoms resolved in 113+/-84 minutes; adverse effects were reported by 12 of the 165 patients who had recurrences (7%), including one atrial flutter at a rapid ventricular rate.
• Funding: not stated.

Limit of this finding: Nobody was randomised and there was no comparison group, so the 94% success rate cannot be separated from episodes that would have settled on their own. The 7% adverse-effect figure is 12 out of the 165 patients who actually had a recurrence, not out of all 210 enrolled. Patients were screened first: 58 of the original 268 were dropped for treatment failure or side effects before this phase began. The reported time to treatment, "36+/-93 minutes", has a spread more than twice its own average, so it should not be read as a typical time.

During a mean follow-up of 15+/-5 months, 165 patients (79 percent) had a total of 618 episodes of arrhythmia; of those episodes, 569 (92 percent) were treated 36+/-93 minutes after the onset of symptoms. Treatment was successful in 534 episodes (94 percent); the time to resolution of symptoms was 113+/-84 minutes. Among the 165 patients with recurrences, the drug was effective during all the arrhythmic episodes in 139 patients (84 percent). Adverse effects were reported during one or more arrhythmic episodes by 12 patients (7 percent), including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac side effects in 11 patients.

Added to a beta-blocker in catecholaminergic polymorphic ventricular tachycardia, flecainide reduced an exercise arrhythmia score in a single-blind placebo-controlled crossover trial of 14 patients. (Source 8)

• Randomized trial, Very low certainty.
• Size: 14 randomised, 13 completed, at 10 US sites.
• Who: patients with clinically diagnosed CPVT and an implantable defibrillator, median age 16 years.
• How long: 3 months per treatment period with a 1-week washout, crossover.
• Result: median exercise ventricular arrhythmia score 0 (range 0-2) on flecainide vs 2.5 (range 0-4) on placebo, P < .01; complete suppression in 11 of 13 (85%); adverse events did not differ.
• Funding: investigator-initiated, multicentre; a midtrial protocol change is reported.

Limit of this finding: This was a single-blind trial, not double-blind, in 14 patients with a mid-trial protocol change, and everyone in it already had an implanted defibrillator and was on the highest beta-blocker dose they could tolerate. The outcome was a 0-to-4 score for arrhythmia seen during an exercise test, not a count of collapses, cardiac arrests or deaths.

The median ventricular arrhythmia score during exercise was significantly reduced by flecainide (0 [range, 0-2] vs 2.5 [range, 0-4] for placebo; P < .01), with complete suppression observed in 11 of 13 patients (85%). Overall and serious adverse events did not differ between the flecainide and placebo arms.

In a 247-patient case cross-over analysis, arrhythmic event rates were lower during the period on flecainide than during the same patients’ earlier period on beta-blocker alone. (Source 16)

• Case-control study, Low certainty.
• Size: 247 patients from two international registries, each serving as their own control.
• Who: patients with clinical or genetic CPVT; median age at flecainide start 18 years, median dose 2.2 mg/kg/day.
• How long: median 2.1 years before flecainide and 2.9 years on flecainide.
• Result: annual event rate 5.6% before flecainide vs 4.0% on flecainide within the same patients; incidence rate ratio 0.55 (95% CI 0.38 to 0.83, P = 0.007); in those who had already had an event on beta-blocker alone, IRR 0.25 (0.14 to 0.45, P < 0.001). There was no concurrent comparison group.
• Funding: not stated; registry-based.

Limit of this finding: This is a before-and-after comparison inside each patient, not a comparison against other people treated differently. Flecainide was added precisely because events were happening, so a fall afterwards is partly what you would expect anyway (regression to the mean), and anything else that changed over the years - care, monitoring, growing up - changed with it. The design has no exact match in our list of study types; "case-control" is the closest, and the paper calls itself a multicentre case cross-over study.

There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007).

What the evidence does not support

The Cochrane authors state there were too few mortality data for flecainide to estimate its mortality risk, while confirming moderate-certainty increases in proarrhythmia and adverse effects. (Source 17)

• Systematic review, Moderate certainty.
• Size: 59 RCTs, 20,981 participants.
• Who: adults after cardioversion of atrial fibrillation.
• How long: mean follow-up 10.2 months.
• Result: no reliable mortality estimate for flecainide; no evidence of benefit on clinical outcomes other than recurrence.
• Funding: Cochrane review; funding not stated in the abstract.

We found few data on mortality in people taking disopyramide, flecainide and propafenone, so it was not possible to make a reliable estimation of the mortality risk for these drugs. However, we did find moderate-certainty evidence of marked increases in proarrhythmia and adverse effects with flecainide.Overall, there is evidence showing that antiarrhythmic drugs increase adverse events, increase proarrhythmic events and some antiarrhythmics may increase mortality. Conversely, although they reduce recurrences of atrial fibrillation, there is no evidence of any benefit on other clinical outcomes, compared with placebo or no treatment.

The label states there is no controlled-trial evidence that flecainide improves survival or reduces sudden death. (Source 5)

• Official position, Certainty not rated.
• Size: not stated.
• Who: patients prescribed flecainide for any indication.
• How long: not stated.
• Result: no survival benefit demonstrated; use in chronic atrial fibrillation not adequately studied and not recommended.
• Funding: not applicable (FDA-approved labelling)

As is the case for other antiarrhythmic agents, there is no evidence from controlled trials that the use of Flecainide Acetate Tablets, USP favorably affects survival or the incidence of sudden death.

Where the evidence is mixed

A meta-analysis of 122 studies in supraventricular arrhythmia without ventricular damage reported low mortality on flecainide, and reported proarrhythmic events in both arms in a sentence whose direction is ambiguous as published. (Source 18)

• Meta-analysis, Low certainty.
• Size: 122 prospective studies, 4,811 patients on flecainide, 2,015 patient-years of exposure.
• Who: patients with supraventricular arrhythmias and no significant signs of ventricular damage; mean age 55 +/- 13 years.
• How long: total exposure 2,015 patient-years; mean oral dose 216 +/- 65 mg/day.
• Result: 8 deaths, total mortality 0.166%, 0.397 per 100 patient-years; 1 death among controls, difference not significant (p = 0.46); proarrhythmic events in 120 patients on flecainide and 88 control patients (p < 0.001) as the abstract words it.
• Funding: not stated; published in a journal with pharmaceutical-industry affiliations - treat with caution.

Limit of this finding: One sentence in this abstract cannot be interpreted as printed. It says proarrhythmic events were seen in 120 patients on flecainide and, "significantly more frequent", in 88 control patients - but 88 is fewer than 120, and the abstract never says how many control patients there were, so there is no way to work out either rate. All it establishes is that both groups had proarrhythmic events and that the authors found a significant difference on numbers they did not publish; it does not establish which group fared worse. The pooled safety picture also rests mostly on uncontrolled series: only 21 of the 122 studies were placebo-controlled.

The total database on flecainide contains the reports of 8 deaths (total mortality 0.166%, mortality rate per 100 patient years 0.397). 3 deaths were non-cardiac deaths (cancer, suicide, urosepsis). Of the cardiac deaths, all but two occurred in patients with coronary heart disease. In controls, there was 1 death. Even for all deaths, this difference was not significant (p = 0.46). Proarrhythmic events were seen in 120 patients on flecainide, and, significantly more frequent, in 88 control patients (p < 0.001).

Where the research disagrees

Whether flecainide is safe in people with supraventricular arrhythmia and no structural heart disease

• Wehling, meta-analysis of 122 prospective studies in 4,811 supraventricular-arrhythmia patients, meta-analysis of 122 prospective studies, of which only 21 were placebo-controlled, so mostly uncontrolled series: The data clearly show that the use of flecainide in patients with supraventricular arrhythmias is safe and, because of its proven efficacy, advisable. Scrutiny should be exercised to diagnose all patients with structural left ventricular damage. (Source 18)
• Valembois and colleagues, Cochrane review of 59 randomised trials, systematic review of randomised controlled trials with GRADE certainty ratings: However, we did find moderate-certainty evidence of marked increases in proarrhythmia and adverse effects with flecainide. (Source 17)

How far the CAST mortality finding generalises beyond people who have recently had a heart attack

• The flecainide boxed warning, FDA-approved labelling interpreting a randomised controlled trial: The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) is uncertain, but at present, it is prudent to consider the risks of Class IC agents (including flecainide acetate), coupled with the lack of any evidence of improved survival, generally unacceptable in patients without life-threatening ventricular arrhythmias, even if the patients are experiencing unpleasant, but not life-threatening, symptoms or signs. (Source 2)
• Alboni and colleagues, 210 selected patients with mild heart disease or none, single-arm feasibility and safety study in a risk-stratified population: Adverse effects were reported during one or more arrhythmic episodes by 12 patients (7 percent), including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac side effects in 11 patients. (Source 7)

How much

• Reference intake: Dosing is set by the prescriber. As a position, the US label (SPL effective 2026-05-29) gives a starting dose of 50 mg every 12 hours for paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation, and 100 mg every 12 hours for sustained ventricular tachycardia, with increases no more often than every four days. (Source 12)
• Upper limit: As a position, the same label sets the maximum for ADULTS at 300 mg a day for paroxysmal supraventricular arrhythmias and 400 mg a day for sustained ventricular tachycardia, and says a loading dose is not recommended. Those two figures are adult ceilings only: the same DOSAGE AND ADMINISTRATION section of the label sets a separate and much lower maximum for children, and a lower starting dose in severe kidney impairment. (Source 12)
• Studied: The CPVT registry cohort used a median dose of 2.2 mg/kg per day (interquartile range 1.7 to 3.1) added to a beta-blocker. (Source 16)
• Studied: The pooled supraventricular safety meta-analysis reported a mean oral dose of 216 +/- 65 mg a day across 84 oral studies. (Source 18)
• Studied: The CPVT randomised trial dosed flecainide twice daily guided by trough serum levels rather than by a fixed milligram amount. (Source 8)

A common belief, and what the research shows

The belief: Flecainide stops palpitations, so it must be protecting the heart and lowering the risk of dying suddenly.

What the research shows: Rhythm control and survival are different things. The label is explicit: "As is the case for other antiarrhythmic agents, there is no evidence from controlled trials that the use of Flecainide Acetate Tablets, USP favorably affects survival or the incidence of sudden death." In CAST, the drug suppressed the ectopic beats and the patients died more often: "This rate was 16/315 (5.1%) for flecainide acetate and 7/309 (2.3%) for the matched placebo." The Cochrane review reaches the same conclusion across all antiarrhythmics: "although they reduce recurrences of atrial fibrillation, there is no evidence of any benefit on other clinical outcomes, compared with placebo or no treatment."

Questions and answers

What is it?

Flecainide acetate is a prescription tablet for abnormal heart rhythms. It belongs to the Class IC antiarrhythmics, which work like local anaesthetics on heart muscle, slowing the electrical impulse. Its strongest effect is on the His-Purkinje conduction system deep in the heart. (Source 1)

What does it do in the body?

It slows conduction through every part of the heart, most of all the His-Purkinje system, which can break the self-sustaining circuits behind atrial fibrillation and supraventricular tachycardia. It also weakens the force of contraction, shown as falls in ejection fraction after single 200 to 250 mg doses. (Source 1)

Is it good or bad for you?

Both, and which one depends entirely on the heart it is given to. In people without structural heart disease it reduces symptomatic atrial fibrillation and supraventricular tachycardia. In people who have recently had a heart attack it killed more patients than placebo, which is why that use is contraindicated and why the warning says the risks of Class IC drugs are generally unacceptable without a life-threatening arrhythmia. (Source 2)

How do you get more of it?

It is prescription-only and there is no food or supplement source. Dose is individualised and raised slowly, no more often than every four days, because the drug takes 3 to 5 days to reach a steady level in the blood. For sustained ventricular tachycardia the label requires treatment to be started in hospital with rhythm monitoring whatever the person’s heart is like. The adult maxima in the label are 300 mg a day for supraventricular arrhythmias and 400 mg a day for sustained ventricular tachycardia, with lower ceilings for children and in kidney impairment. That is a record of the label, not a recommendation. (Source 12)

If it is harmful, what reduces it?

Flecainide leaves the body partly unchanged in urine and partly after liver metabolism by CYP2D6, with a half-life of about 12 to 27 hours. Dialysis does not remove it. In overdose with strongly alkaline urine, acidifying the urine has been suggested in theory, but the label says there is no evidence that acidifying normal urine helps. (Source 11)

Why might someone be low in it or missing it?

Does not apply as a deficiency: flecainide is a manufactured drug, not a nutrient. Someone may be unable to take it because of what their heart is like. The label says it should not be used after a recent heart attack, is not recommended in chronic atrial fibrillation, and is not recommended for less severe ventricular arrhythmias even when symptomatic. (Source 5)

Which whole foods contain it or feed it?

No food contains flecainide. Two dietary points are documented on the label. Ordinary food and antacids do not change absorption in adults. Milk does reduce absorption in infants, enough that the label asks for a dose reduction if milk is taken out of an infant’s diet, and a strict vegetarian diet can make urine alkaline enough to slow elimination. (Source 10)

What happens if you do not have it?

For most people, nothing: the body has no need of it. For someone whose symptomatic arrhythmia it was controlling, episodes come back, and they were coming back anyway in a large minority of treated people. The Cochrane review found atrial fibrillation still recurred in 43% to 67% of people taking an antiarrhythmic. (Source 3)

How can you test for it?

Flecainide can be measured in blood and the label gives a range: about 0.2 to 1 microgram per millilitre of plasma for maximal therapeutic effect, with levels above 0.7 to 1 linked to more conduction problems and slow heart rates. The label is careful about what a level does not tell you - it says the relation between plasma level and dangerous rhythm disturbance is not established. The other monitoring is electrical: an ECG, and in-hospital initiation with rhythm monitoring for sustained ventricular tachycardia. (Source 1)

References

1. DailyMed / US FDA Structured Product Label (EPIC PHARMA, LLC, SPL effective 2026-05-29). Flecainide Acetate Tablets, USP - CLINICAL PHARMACOLOGY, Electrophysiology. 2026. Read the source
2. DailyMed / US FDA Structured Product Label (EPIC PHARMA, LLC, SPL effective 2026-05-29). Flecainide Acetate Tablets, USP - FDA prescribing information (boxed warning section, LOINC 34066-1). 2026. Read the source
3. Cochrane Database of Systematic Reviews. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. (Main results: recurrence of atrial fibrillation). 2019. PMID 31483500, DOI 10.1002/14651858.CD005049.pub5. Read the source
4. American Journal of Cardiology. Flecainide acetate for paroxysmal supraventricular tachyarrhythmias. The Flecainide Supraventricular Tachycardia Study Group.. 1994. PMID 8074041, DOI 10.1016/0002-9149(94)90747-1. Read the source
5. DailyMed / US FDA Structured Product Label (EPIC PHARMA, LLC, SPL effective 2026-05-29). Flecainide Acetate Tablets, USP - INDICATIONS AND USAGE. 2026. Read the source
6. New England Journal of Medicine. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial.. 1991. PMID 1900101, DOI 10.1056/NEJM199103213241201. Read the source
7. New England Journal of Medicine. Outpatient treatment of recent-onset atrial fibrillation with the "pill-in-the-pocket" approach.. 2004. PMID 15575054, DOI 10.1056/NEJMoa041233. Read the source
8. JAMA Cardiology. Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: A Randomized Clinical Trial.. 2017. PMID 28492868, DOI 10.1001/jamacardio.2017.1320. Read the source
9. DailyMed / US FDA Structured Product Label (EPIC PHARMA, LLC, SPL effective 2026-05-29). Flecainide Acetate Tablets, USP - PRECAUTIONS, Drug Interactions. 2026. Read the source
10. DailyMed / US FDA Structured Product Label (EPIC PHARMA, LLC, SPL effective 2026-05-29). Flecainide Acetate Tablets, USP - CLINICAL PHARMACOLOGY, Metabolism in Humans. 2026. Read the source
11. DailyMed / US FDA Structured Product Label (EPIC PHARMA, LLC, SPL effective 2026-05-29). Flecainide Acetate Tablets, USP - CLINICAL PHARMACOLOGY, elimination and urinary pH. 2026. Read the source
12. DailyMed / US FDA Structured Product Label (EPIC PHARMA, LLC, SPL effective 2026-05-29). Flecainide Acetate Tablets, USP - DOSAGE AND ADMINISTRATION. 2026. Read the source
13. DailyMed / US FDA Structured Product Label (EPIC PHARMA, LLC, SPL effective 2026-05-29). Flecainide Acetate Tablets, USP - ADVERSE REACTIONS. 2026. Read the source
14. Cochrane Database of Systematic Reviews. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation.. 2019. PMID 31483500, DOI 10.1002/14651858.CD005049.pub5. Read the source
15. DailyMed / US FDA Structured Product Label (EPIC PHARMA, LLC, SPL effective 2026-05-29). Flecainide Acetate Tablets, USP - DOSAGE AND ADMINISTRATION, pediatric and renal-impairment dosing. 2026. Read the source
16. Circulation. Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.. 2023. PMID 37886885, DOI 10.1161/CIRCULATIONAHA.123.064786. Read the source
17. Cochrane Database of Systematic Reviews. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. (Authors' conclusions). 2019. PMID 31483500, DOI 10.1002/14651858.CD005049.pub5. Read the source
18. Arzneimittelforschung. Meta-analysis of flecainide safety in patients with supraventricular arrhythmias.. 2002. PMID 12189773, DOI 10.1055/s-0031-1299923. Read the source