Flecainide

Flecainide is an antiarrhythmic Class 1 C agent belonging to a Sodium channel blocker.

Flecainide is used in the treatment of paroxysmal supraventricular tachycardia (PSVTs), Ventricular arrhythmias. It is also used in the treatment of Atrial fibrillation or flutter (pharmacologic cardioversion), Fetal tachycardia, and sustained; Ventricular premature beats.

Flecainide is almost completely absorbed and with decreased absorption w/ milk. It crosses the placenta and is distributed in breast milk. The volume of distribution: 5.5 -8.7 L/kg (oral); approx 10 L/kg (IV) with plasma protein binding: Approx 40% and get converted into m-O-dealkylated Flecainide and m-O-dealkylated lactam of Flecainide by the CYP2D6 isoenzyme, subjected to genetic polymorphism. It gets excreted Via urine (30% as unchanged drug and the remainder as metabolites) and feces (5%).

The common side effects are Headaches, Feeling drowsy, sleepy, or dizzy, Feeling nervous, unsteady, or shaky, Feeling or being sick (nausea or vomiting), Constipation, and Sore or swollen gums.

Flecainide is available in the form of a dosage form such as Tablets.

Flecainide is available in Europe, India, Japan, and the U.S.

Flecainide, an amide anesthetic, belongs to Class Ic antiarrhythmic agents. It inhibits the transmembrane influx of extracellular Na ions via fast channels on cardiac tissues resulting in a decrease in the rate of depolarisation of the action potential, prolonging the PR and QRS intervals. At high concentrations, it exerts inhibitory effects on slow Ca channels, accompanied by a moderate negative inotropic effect.

The Duration of Action of Flecainide was within 12-13 hours.

The Tmax was about 3-4 hr, and Cmax was approximate> 200 ng/mL.

Flecainide is available in the form of Tablets.

Oral: When used for the management of fetal tachycardia (maternal/transplacental administration; off-label use), oral doses are administered to the mother.

Flecainide is used in the treatment of paroxysmal supraventricular tachycardia (PSVTs), Ventricular arrhythmias. It is also used in the treatment of Atrial fibrillation or flutter (pharmacologic cardioversion); Fetal tachycardia, and sustained; Ventricular premature beats.

Flecainide is an antiarrhythmic agent (Class Ic). flecainide has a fast onset and offsets kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. It shortens the action potential duration, reduces refractoriness.

● Paroxysmal atrial fibrillation/flutter and paroxysmal supraventricular tachycardias (prevention): Prevention of paroxysmal atrial fibrillation/flutter associated with disabling symptoms and paroxysmal supraventricular tachycardias (PSVT), including atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, and other supraventricular tachycardias of unspecified mechanism associated with disabling symptoms in patients without structural heart disease.

● Ventricular arrhythmias (prevention): Prevention of documented life-threatening ventricular tachyarrhythmias (eg, sustained ventricular tachycardia) in patients without structural heart disease.

● Limitations of use: Use of Flecainide is not recommended in patients with less severe ventricular arrhythmias, even if symptomatic. Because of the proarrhythmic effects of Flecainide, its use should be reserved for patients in whom the benefits of treatment outweigh the risks. Flecainide should not be used in patients with permanent atrial fibrillation (not adequately studied) or recent myocardial infarction. No evidence from controlled trials have demonstrated favorable effects of Flecainide on survival or the incidence of sudden death.

• Although not approved there have been certain off label use documented for Flecainide which includes:-

Atrial fibrillation or flutter (pharmacologic cardioversion); Fetal tachycardia, sustained; Ventricular premature beats

The dosage and the duration of treatment should be as per the clinical judgment of the treating physician.

Flecainide is available in various dosage strengths 50 mg, 100 mg, 150 mg

Flecainide is available in the form of tablets

• Dose Adjustment in Kidney patient:

There are no dosage adjustments provided ; however, elimination from the plasma may be slower in patients with hepatic impairment. Use with caution; obtain plasma concentrations to guide dosage adjustments. Dose increases should be made very cautiously at intervals >4 days and serum concentrations monitored frequently. Frequent plasma level monitoring is required in patients with severe hepatic impairment; if unavailable, use is not recommended.

• Dose Adjustment in Hepatic Impairment Patient:

There are no dosage adjustments provided; however, elimination from the plasma may be slower in patients with hepatic impairment. Use with caution; obtain plasma concentrations to guide dosage adjustments. Dose increases should be made very cautiously at intervals >4 days and serum concentrations monitored frequently. Frequent plasma level monitoring is required in patients with severe hepatic impairment; if unavailable, use is not recommended.

• Dose Adjustment in the pediatric patient:

Arrhythmias:

BSA-directed dosing: Use caution with dose titration, as small change in dose may result in a disproportionate increase in plasma concentrations.

Infants ≤6 months: Oral: Initial: 50 mg/m2/day divided every 8 to 12 hours; may titrate dose at 4-day intervals; maximum daily dose: 200 mg/m2/day; higher doses have been associated with an increased risk of proarrhythmic effects.

Infants >6 months, Children, and Adolescents: Oral: Initial: 100 mg/m2/day divided every 8 to 12 hours; may titrate dose at 4-day intervals; maximum daily dose: 200 mg/m2/day; higher doses have been associated with an increased risk of proarrhythmic effects.

Weight-based dosing: Limited data available; dosing regimens variable: Infants, Children, and Adolescents: Oral: Initial: 1 to 3 mg/kg/day divided every 8 hours; may titrate dose at 4-day intervals; usual maintenance range: 3 to 6 mg/kg/day ; an average effective dose of 4 mg/kg/day was reported in an expert analysis of literature and clinical experience; maximum daily dose: 8 mg/kg/day; higher doses have been associated with an increased risk of proarrhythmic effects.

Flecainide is used in the treatment of paroxysmal supraventricular tachycardia (PSVTs), Ventricular arrhythmias. It is also used in the treatment of Atrial fibrillation or flutter (pharmacologic cardioversion); Fetal tachycardia, sustained; Ventricular premature beats.

Ventricular Arrhythmias:

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Diets high in processed foods, such as fast food, and items high in added sugar, like soda and sugary baked goods, have been linked to increased heart disease risk

The dietary restriction should be individualized as per the patient requirements.

Flecainide may be contraindicated in the Heart failure

• Hypersensitivity to Flecainide or any component of the formulation; pre-existing second- or third-degree AV block or with right bundle branch block when associated with a left hemiblock (bifascicular block) (except in patients with a functioning artificial pacemaker); cardiogenic shock; concurrent use of ritonavir.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

Disease-related concerns:

• AV block: If second or third-degree AV block, or right bundle branch block associated with a left hemiblock occur, flecainide therapy should be discontinued unless a temporary or implanted ventricular pacemaker is in place to ensure an adequate ventricular rate.

• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.

• Hepatic impairment: Use with caution in patients with significant hepatic impairment; benefit should outweigh risk. Consider careful monitoring during initiation of therapy. Dose titration should occur only after steady state has been achieved (≥4 days after initiation). Frequent plasma level monitoring is required in patients with severe hepatic impairment; if unavailable, use is not recommended.

• Renal impairment: Use with caution in patients with significant renal impairment. Frequent plasma level monitoring is required in patients with severe renal impairment; if unavailable, use is not recommended.

• Structural or ischemic heart disease: According to the manufacturer, use with extreme caution in patients with structural heart disease as the risk of death and cardiac events may be increased. Avoid use in patients with structural or ischemic heart disease (ACC/AHA/HRS [Page 2015]).

Special populations:

• Pediatric: Small changes in dose may lead to disproportionate increases in plasma concentrations in pediatric patients. Following initiation of therapy or changes in dose, obtain plasma trough concentrations and ECG once steady state has been achieved (>5 doses after initiation or change); regular monitoring of trough concentrations and ECG is recommended by the manufacturer during the first year of therapy and during major changes in dietary milk intake as milk may interfere with the absorption of Flecainide in pediatric patients (Russell 1989; Thompson 2012; manufacturer's labeling); consider dose reductions when milk is removed from the diet (eg, during weaning or bouts of gastroenteritis).

Alcohol consumption with Flecainide may increase the risk of low blood pressure and cause adverse effects, such as Dizziness, fainting, light-headedness, or headache.

Flecainide use in breastfeeding patients is not recommended.

Pregnancy Category X

Risk Summary

Flecainide may cause fetal harm when administered to a pregnant woman and is contraindicated during pregnancy.

"Flecainide "was teratogenic and embryotoxic in rats at doses with exposures to an unbound drug that were approximately 8 Times and 2 times, respectively, the human exposure. In rabbits, Flecainide led to abortions at 4 times the human exposure and fetal toxicity with exposures approximately 13 times the human exposure. If Flecainide is used in pregnancy, or if the Patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus .

Clearance may be decreased in patients following strict vegetarian diets due to urinary pH ≥8. Milk may interfere with the absorption of Flecainide (Russell 1989; Thompson 2012). Management: Dose reduction should be considered when milk is removed from the diet (eg, during weaning or bouts of gastroenteritis). Plasma trough flecainide levels should be monitored during major changes in dietary milk intake.

The adverse reactions related to molecule Flecainide.

• Common Adverse effects:

Pro-arrhythmic effects, dizziness, visual disturbances, lightheadedness, giddiness, nausea, vomiting, headache, tremor, peripheral neuropathy, ataxia, paraesthesia, hypoaesthesia.

• Less Common Adverse effects:

Hyperhidrosis, syncope, tremor, vertigo, flushing, somnolence, tinnitus, increased sweating, depression, anxiety, insomnia, photosensitivity, and mild blood cells reduction.

• Rare Adverse effects:

Hallucinations, amnesia, confusion, depression, dyskinesia, convulsion, urticaria, chest pain, elevated liver enzyme.

The clinically relevant drug interactions of Flecainide is briefly summarized here.

Flecainide is extensively bound to plasma proteins and is prone to competitive displacement. flecainide is metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19 and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating flecainide concentrations and enhance the risk of drug toxicity.

Monitoring of flecainide serum levels is recommended when a drug interaction is suspected.

Pediatric Use

Safety and effectiveness in pediatric patients have been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Symptoms:

Nausea and vomiting, convulsion, hypotension, bradycardia, widening of PR and QT intervals, ventricular tachycardia, AV nodal block, bundle branch block, asystole, cardiac and resp failures.

Management:

Symptomatic and supportive treatment. Neotropics (e.g. dopamine, dobutamine, isoproterenol), mechanical ventilation, and circulatory assistance (e.g. balloon pumping) may also be given.

Pharmacodynamics:

Flecainide, an amide anaesthetic, belongs to Class Ic antiarrhythmic agents. It inhibits the transmembrane influx of extracellular Na ions via fast channels on cardiac tissues resulting to a decrease in the rate of depolarisation of the action potential, prolonging the PR and QRS intervals. At high concentrations, it exerts inhibitory effects on slow Ca channels, accompanied by moderate negative inotropic effect.

Pharmacokinetics:

• Absorption: Almost completely absorbed. Decreased absorption w/ milk. Bioavailability: Approx 90%. Time to peak plasma concentration: Approx 3 hr.
• Distribution: Crosses the placenta and distributed in breast milk. Volume of distribution: 5.5 -8.7 L/kg (oral); approx 10 L/kg (IV). Plasma protein binding: Approx 40%.
• Metabolism: Converted into m-O-dealkylated Flecainide and m-O-dealkylated lactam of Flecainide by CYP2D6 isoenzyme, subjected to genetic polymorphism.
• Excretion: Via urine (30% as unchanged drug and the remainder as metabolites) and faeces (5%). Elimination half-life: Approx 20 hr.

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036302/
• https://www.ahajournals.org/doi/10.1161/CIRCEP.121.010204
• https://www.ncbi.nlm.nih.gov/books/NBK542291/#:~:text=Flecainide acetate is an oral,received FDA approval in 1984.
• https://go.drugbank.com/drugs/DB01195