Absorption, Distribution and Excretion
Oral flecainide has a Tmax of 3-4h and a bioavialability of 90%. Taking flecainide with food or aluminum hydroxide antacids do not significantly affect the absorption of flecainide.
Approximately 86% of a single oral dose is eliminated in the urine, with 42% as unchanged flecainide and 14% as meta-O-dealkylated flecainide, a similar amount of the meta-O-dealkylated lactam of flecainide, approximately 3% as an unidentified acid metabolite, and <1% as 2 other unknown metabolites. 5% is eliminated in the feces.
The average volume of distribution in 8 male subjects is 5.0-13.4L/kg.
The average clearance of intravenous flecainide is 4.6-12.1mL/min/kg in 8 male subjects. For oral flecainide, the clearance was 4-20mL/min/kg.

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Metabolism / Metabolites
Flecainide is mainly metabolized to meta-O-dealkylated flecainide or the meta-O-dealkylated lactam of flecainide. Meta-O-dealkylated flecainide has 20% the activity of flecainide. Both of these metabolites are generally detected as glucuronide or sulfate conjugates. Flecainide’s metabolism involves the action of CYP2D6 and CYP1A2.
Hepatic. Flecainide does not undergo any consequential presystemic biotransformation. The two major urinary metabolites are meta-O-dealkylated flecainide (active, but about one-fifth as potent) and the meta-O-dealkylated lactam of flecainide (non-active metabolite). The absoprtion is nearly complete following oral administration. Hepatic. Flecainide does not undergo any consequential presystemic biotransformation. The two major urinary metabolites are meta-O-dealkylated flecainide (active, but about one-fifth as potent) and the meta-O-dealkylated lactam of flecainide (non-active metabolite).
Route of Elimination: In healthy subjects, about 30% of a single oral dose (range, 10 to 50%) is excreted in urine as unchanged drug. Several minor metabolites (3% of the dose or less) are also found in urine; only 5% of an oral dose is excreted in feces. In patients, free (unconjugated) plasma levels of the two major metabolites are very low (less than 0.05 ug/mL).
Half Life: 20 hours (range 12-27 hours)

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Biological Half-Life
In healthy subjects, intravenous flecainide has an average half life of 13 hours for a single dose and 16 hours for multiple oral doses. In patients with a ventricular premature complex, flecainide has a half life of 20 hours. The half life of meta-O-dealkylated flecainide, a major metabolite of flecainide, is 12.6h.

Toxicity Summary
Flecainide acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers. Flecainide is a sodium channel blocker, binding to voltage gated sodium channels. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole.

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Hepatotoxicity
In clinical trials, flecainide was associated with a low rate of serum aminotransferase and alkaline phosphatase elevations. Despite wide scale use, flecainide has only rarely been linked to cases of clinically apparent liver injury. The typical presentation is with a cholestatic hepatitis arising within 1 to 6 weeks of starting flecainide. In addition, instances of acute hepatic injury arising within 1 to 3 days of starting flecainide with marked, but short lived elevations in serum aminotransferase levels and minimal increases in alkaline phosphatase have been published, but may actually represent acute worsening of congestive heart failure and ischemic hepatitis due to the proarrhythmic effects of flecainide. In all instances, the liver injury was self limited. Immunoallergic and autoimmune features were not present.
Likelihood score: C (probable rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Maternal doses of flecainide up to 200 mg daily produce low levels in milk and undetectable infant serum levels. Flecainide is not expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months.
◉ Effects in Breastfed Infants
A woman with ventricular arrhythmia was treated with flecainide 87.3 mg twice daily during pregnancy and postpartum and exclusively breastfed her infant. Her infant was followed weekly with electrocardiograms until about 6 months of age. All were normal.
Eight breastfed infants of mothers taking flecainide were followed after inquiries by their mothers. The extent of breastfeeding was exclusive in 2 infants, mixed in 5 and unknown in 1. The median maternal flecainide dose was 150 mg (IQR 100 to 175 mg). Clinical examination at day 15 of life was normal in all infants, electrocardiograms in 2 were normal, and none of the 8 infants had an adverse effect. Two children who breastfed for 5 and 8 months, were healthy and developed normally at 1 and 2 years of age, respectively.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Flecainide is 40% bound to protein in serum, mainly to alpha-1-acid glycoprotein and minorly 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 obtained by formal condensation of the carboxy group of 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid with the primary amino group of piperidin-2-ylmethylamine. An antiarrhythmic agent used (in the form of its acetate salt) to prevent and treat tachyarrhythmia (abnormal fast rhythm of the heart). It has a role as an anti-arrhythmia drug. It is a monocarboxylic acid amide, a member of piperidines, an organofluorine compound and an aromatic ether. It is a conjugate base of a flecainide(1+).
Flecainide is a Class I anti-arrhythmic agent like [encainide] and [propafenone]. Flecainide’s development began in 1966 and was first synthesized in 1972 as an attempt to generate new anesthetics. It is used to prevent supraventricular and ventricular arrhythmias, as well as paroxysmal atrial fibrillation and flutter. Flecainide was granted FDA approval on 31 October 1985.
Flecainide is an Antiarrhythmic.
Flecainide is an oral antiarrhythmic agent that has been in use for several decades. Long term flecainide therapy is associated with a low rate of serum enzyme elevations and is a very rare cause of clinically apparent acute liver injury.
Flecainide is a synthetic agent derived from trifluoroethoxy-benzamide exhibiting antiarrhythmic and local anesthetic activity. As a class Ic antiarrhythmic that blocks sodium channels, flecainide depresses polarization phase 0 and decreases the induction velocity of the His-Purkinje system. It also decreases phase 4 slope and increases the depolarization threshold. (NCI04)
A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias. Paradoxically, however, in myocardial infarct patients with either symptomatic or asymptomatic arrhythmia, flecainide exacerbates the arrhythmia and is not recommended for use in these patients. [PubChem]
A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.
See also: Flecainide Acetate (has salt form).

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Drug Indication
In New Zealand and America, flecainide is indicated to prevent supraventricular arrhythmias and ventricular arrhythmias. In the United States, it is also indicated to prevent paroxysmal atrial fibrillation and flutter.

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Mechanism of Action
Flecainide blocks fast inward sodium channels and slowly unbinds during diastole, prolonging the refractory period of the heart. This blockade also shortens the duration of action potentials through the Purkinjie fibers. Flecainide also prevents delayed rectifier potassium channels from opening, lengthening the action potential through ventricular and atrial muscle fibers. Finally, flecainide also blocks ryanodine receptor opening, reducing calcium release from sarcoplasmic reticulum, which reduces depolarization of cells.

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Pharmacodynamics
Flecainide inhibits the action of sodium and potassium ion channels in the heart, raising the threshold for depolarization and correcting arrhythmias. Flecainide has a long duration of action, allowing for once daily dosing. The therapeutic index is narrow. Patients should not take this medication if there is already 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.)