Absorption, Distribution and Excretion
The time to peak concentration (Tmax) of oral flecainide is 3–4 hours, with a bioavailability of 90%. Co-administration with food or aluminum hydroxide antacids does not significantly affect flecainide absorption. Approximately 86% of a single oral dose is excreted in the urine, including 42% unchanged flecainide, 14% meta-O-dealkylated flecainide, 14% meta-O-dealkylated flecainide lactam, approximately 3% unidentified acidic metabolites, and <1% two other unknown metabolites. 5% is excreted in the feces. The mean volume of distribution in 8 male subjects was 5.0–13.4 L/kg. The mean clearance of intravenously administered flecainide in 8 male subjects was 4.6–12.1 mL/min/kg. The clearance of orally administered flecainide was 4–20 mL/min/kg.

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Metabolism/Metabolites
Flecainide is primarily metabolized to meta-O-dealkylated flecainide or meta-O-dealkylated flecainilamide. The activity of meta-O-dealkylated flecainide is approximately 20% of that of flecainide. Both metabolites are usually detected as glucuronide or sulfate conjugates. The metabolism of flecainide involves the action of CYP2D6 and CYP1A2.
Hepatic metabolism. Flecainide does not undergo any significant first-pass biotransformation. The two main urinary metabolites are meta-O-dealkylated flecainide (active, but with approximately one-fifth the potency of the parent drug) and meta-O-dealkylated flecainilamide (inactive metabolite). Absorption after oral administration is almost complete. It is primarily metabolized by the liver. Flecainide does not undergo any significant first-pass biotransformation. The two main urinary metabolites are meta-O-dealkylated flecainide (active, but with approximately one-fifth the potency of the original drug) and meta-O-dealkylated flecainide lactam (inactive metabolite).
Excretion route: In healthy subjects, approximately 30% (range: 10% to 50%) of a single oral dose is excreted unchanged in the urine. Several minor metabolites are also present in the urine (3% or less of the dose). Only 5% of the oral dose is excreted in the feces. In patients, the free (unbound) plasma concentrations of the two main metabolites are extremely low (below 0.05 μg/mL).
Half-life: 20 hours (range 12–27 hours)
Biological half-life
In healthy subjects, the mean half-life of flecainide after a single intravenous injection is 13 hours, and the mean half-life after multiple oral administrations is 16 hours. In patients with premature ventricular contractions (PVCs), the half-life of flecainide is 20 hours. The major metabolite of flecainide, meta-O-dealkylated flecainide, has a half-life of 12.6 hours.

Toxicity Summary
Flecainide acts on sodium channels in neuronal cell membranes, limiting the spread of epileptic activity and reducing the propagation of seizures. Its antiarrhythmic effect is achieved by affecting sodium channels in Purkinje fibers. Flecainide is a sodium channel blocker that binds to voltage-gated sodium channels. It stabilizes the neuronal membrane by inhibiting the ion flow required to initiate and conduct impulses. Ventricular excitability is reduced, and the diastolic ventricular stimulation threshold is increased. Hepatotoxicity
In clinical trials, flecainide was associated with a low incidence of elevated serum transaminases and alkaline phosphatase. Despite its widespread use, only a very small number of cases have been associated with clinically significant liver injury. The typical presentation is cholestatic hepatitis, which usually appears within 1 to 6 weeks after starting flecainide treatment. Furthermore, existing literature reports acute liver injury within 1 to 3 days after flecainide administration, manifested as a significant but transient increase in serum transaminase levels and a slight increase in alkaline phosphatase levels. However, these conditions may actually represent an acute exacerbation of congestive heart failure and ischemic hepatitis due to the arrhythmogenic effects of flecainide. All cases of liver injury were self-limiting, and no immune hypersensitivity or autoimmune features were observed. Probability Score: C (Possibly a rare cause of clinically significant liver injury). Pregnancy and Lactation Use ◉ Overview of Lactation Use When pregnant women take up to 200 mg of flecainide daily, the drug concentration in breast milk is low, and the drug concentration in infant serum is undetectable. Flecainide is not expected to cause any adverse reactions in breastfed infants, especially those older than 2 months.
◉ Effects on Breastfed Infants
A woman with ventricular arrhythmia received flecainide treatment during pregnancy and postpartum at a dose of 87.3 mg twice daily and exclusively breastfed her infant. Her infant underwent weekly electrocardiograms until approximately 6 months of age. All results were normal.
Following interviews with mothers taking flecainide, we followed up with 8 breastfed infants. Two infants were exclusively breastfed, five were mixed-fed, and the feeding method for one infant was unknown. The median dose of flecainide taken by the mothers was 150 mg (interquartile range 100–175 mg). All infants had normal clinical findings by day 15 of age, with two infants showing normal electrocardiogram results, and none of the 8 infants experiencing adverse reactions. Two children, breastfed for 5 and 8 months respectively, were healthy and developing normally at 1 and 2 years of age, respectively.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein Binding
Flecainide binds to proteins in serum at a rate of 40%, primarily to α-1-acid glycoprotein, with a small amount binding to serum albumin.

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Toxicity Data
LD50: 50-498 mg/kg (oral, rat) (A308)

[1].Flecainide inhibits the transient outward current in atrial myocytes isolated from the rabbit heart. J Pharmacol Exp Ther. 1995 Jul;274(1):315-21.

[2].Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block. J Physiol. 2004 Jan 15;554(Pt 2):321-34.

[3].Oral flecainide is effective in management of refractory tachycardia in infants. Indian Heart J. 2013 Mar-Apr;65(2):168-71.

Flecainide is a monocarboxylic acid amide formed by the condensation of the carboxyl group of 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid with the primary amino group of piperidine-2-ylmethylamine. It is an antiarrhythmic drug (used in acetate form) used to prevent and treat tachyarrhythmias (abnormally rapid heart rhythms). It is a monocarboxylic acid amide, belonging to the piperidine class of compounds, an organofluorine compound, and an aromatic ether. It is the conjugate base of flecainide (1+). Like encainide and propafenone, flecainide belongs to Class I antiarrhythmic drugs. Research on flecainide began in 1966, and it was first synthesized in 1972, initially for the development of novel anesthetics. It is used to prevent supraventricular and ventricular arrhythmias, as well as paroxysmal atrial fibrillation and atrial flutter. Flecainide was approved by the U.S. Food and Drug Administration (FDA) on October 31, 1985.
Flecainide is an antiarrhythmic drug.
Flecainide is an oral antiarrhythmic drug that has been used for decades. Long-term use of flecainide treatment results in a low incidence of elevated serum enzymes and rarely causes clinically significant acute liver injury.
Flecainide is a synthetic drug derived from trifluoroethoxybenzamide and possesses antiarrhythmic and local anesthetic activities. As a class Ic antiarrhythmic drug that blocks sodium channels, flecainide inhibits phase 0 polarization and reduces the induction rate of the His-Purkinje system. It can also reduce the phase 4 slope and increase the depolarization threshold. (NCI04)
A potent antiarrhythmic drug effective against a variety of ventricular and atrial arrhythmias and tachycardias. However, paradoxically, flecainide can worsen arrhythmias in patients with symptomatic or asymptomatic arrhythmias due to myocardial infarction, and therefore is not recommended for use in such patients. [PubChem]
A potent antiarrhythmic drug effective against a variety of ventricular and atrial arrhythmias and tachycardias.
See also: flecainide acetate (in salt form).
Indications
In New Zealand and the United States, flecainide is indicated for the prevention of supraventricular and ventricular arrhythmias. In the United States, it is also indicated for the prevention of paroxysmal atrial fibrillation and atrial flutter.
Mechanism of Action
Flecainide blocks rapidly inward sodium channels and slowly dissociates them during diastole, prolonging the cardiac refractory period. This blocking effect also shortens the action potential duration of Purkinje fibers. Flecainide also prevents the opening of delayed rectifier potassium channels, thereby prolonging the action potential duration of ventricular and atrial myocardial fibers. In addition, flecainide blocks the opening of rennet receptors, reducing the release of calcium ions from the sarcoplasmic reticulum, thereby reducing cellular depolarization.

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Pharmacodynamics
Flecainide inhibits the activity of sodium and potassium ion channels in the heart, raising the depolarization threshold and thus correcting arrhythmias. Flecainide has a long duration of action, therefore it can be administered once daily. The therapeutic index of this drug is narrow. This drug should not be taken by patients with pre-existing structural heart disease or left ventricular systolic dysfunction.

C17H20N2O3F6

414.3427

414.138

54143-55-4

Flecainide hydrochloride;57415-44-8;Flecainide-d3;127413-31-4

3356

White to off-white solid powder

1.286 g/cm3

434.9ºC at 760 mmHg

105-1070C

216.8ºC

4.16

2

10

7

28

500

0

DJBNUMBKLMJRSA-UHFFFAOYSA-N

InChI=1S/C17H20F6N2O3/c18-16(19,20)9-27-12-4-5-14(28-10-17(21,22)23)13(7-12)15(26)25-8-11-3-1-2-6-24-11/h4-5,7,11,24H,1-3,6,8-10H2,(H,25,26)

N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide

Flecainide, Flecainida, Flecainidum, Tambocor, Apocard

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~241.35 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)