QuickView for flecainide (compound)

Summary
General Info

PubChem

PubChem Compound 3356

Name:	Flecainide
PubChem Compound ID:	3356
Description:	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.
Molecular formula:	C₁₇H₂₀F₆N₂O₃
Molecular weight:	414.343 g/mol
Synonyms:	N-(2-Piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide; Flecaine; Bio2_000517; Flecainida [INN-Spanish]; Bio1_000864; KBio2_000037; SPBio_002629; KBioGR_000037; CCRIS 313; KBio3_000073. show more » N-(2-Piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide; Flecaine; Bio2_000517; Flecainida [INN-Spanish]; Bio1_000864; KBio2_000037; SPBio_002629; KBioGR_000037; CCRIS 313; KBio3_000073; Bio1_001353; KBio3_000074; (+-)-Flecainide; KBioSS_000037; Benzamide, N-(2-piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)-; NSC719273; KBio2_002605; 54143-55-4; Flecainidum [INN-Latin]; C07001; Bio2_000037; 54143-56-5; Bio1_000375; Flecainide; Prestwick0_000735; 99495-87-1; Prestwick1_000735; KBio2_005173 show less «

DrugBank

Identification

Name:	Flecainide
Name (isomeric):	DB01195
Drug Type:	small molecule
Description:	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.
Synonyms:	Flecainida [INN-Spanish]; Flecainidum [INN-Latin]; Flecainide acetate
Brand:	Tambocor, Flecaine
Category:	Antiarrhythmic Agents, Anti-Arrhythmia Agents
CAS number:	54143-55-4

Pharmacology

Indication:	Flecainide is is a class Ic antiarrhythmic agent and as such, it is used for the prevention of paroxysmal supraventricular tachycardias (PSVT), including atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia and other supraventricular tachycardias of unspecified mechanism associated with disablin.
Pharmacology:	Flecainide has local anesthetic activity and belongs to the membrane stabilizing (Class 1) group of antiarrhythmic agents; it has electrophysiologic effects characteristic of the IC class of antiarrhythmics.
Mechanism of Action:	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 membra... show more » 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. show less «
Absorption:	Nearly complete following oral administration.
Protein binding:	40%
Biotransformation:	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 μg/mL).
Half Life:	20 hours (range 12-27 hours)
Toxicity:	Oral LD50 is 50-498 mg/kg in rat. Symptoms of overdose include nausea and vomiting, convulsions, hypotension, bradycardia, syncope, extreme widening of the QRS complex, widening of the QT interval, widening of the PR interval, ventricular tachycardia, AV nodal block, asystole, bundle branch block, cardiac failure, and cardiac arrest.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take without regard to meals.

Drug interaction:

Duloxetine	Possible increase in the levels of this agent when used with duloxetine
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Terfenadine	Increased risk of cardiotoxicity and arrhythmias

Duloxetine	Possible increase in the levels of this agent when used with duloxetine
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Cimetidine	Cimetidine, a moderate CYP2D6 inhibitor, may decrease the metabolism of flecainide.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Quinupristin	This combination presents an increased risk of toxicity
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tipranavir	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Flecainide. Concomitant therapy is contraindicated.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Trimipramine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Ritonavir	Ritonavir increases the toxicity of the anti-arrhythmic
Terbinafine	Terbinafine may reduce the metabolism and clearance of Flecainide. Consider alternate therapy or monitor for therapeutic/adverse effects of Flecainide if Terbinafine is initiated, discontinued or dose changed.
Amiodarone	Amiodarone may increase the effect and toxicity of flecainide
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

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Targets

Sodium channel protein type 5 subunit alpha

This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram

UniProt ID:

Q14524

Gene:

SCN5A

Actions:

inhibitor

References:

Nagatomo T, January CT, Makielski JC: Preferential block of late sodium current in the LQT3 DeltaKPQ mutant by the class I(C) antiarrhythmic flecainide. Mol Pharmacol. 2000 Jan;57(1):101-7.
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Benhorin J, Taub R, Goldmit M, Kerem B, Kass RS, Windman I, Medina A: Effects of flecainide in patients with new SCN5A mutation: mutation-specific therapy for long-QT syndrome? Circulation. 2000 Apr 11;101(14):1698-706.
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Priori SG, Napolitano C, Schwartz PJ, Bloise R, Crotti L, Ronchetti E: The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge. Circulation. 2000 Aug 29;102(9):945-7.
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Cerrone M, Crotti L, Faggiano G, De Michelis V, Napolitano C, Schwartz PJ, Priori SG: [Long QT syndrome and Brugada syndrome: 2 aspects of the same disease?] Ital Heart J Suppl. 2001 Mar;2(3):253-7.
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Viswanathan PC, Bezzina CR, George AL Jr, Roden DM, Wilde AA, Balser JR: Gating-dependent mechanisms for flecainide action in SCN5A-linked arrhythmia syndromes. Circulation. 2001 Sep 4;104(10):1200-5.
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Ramos E, O'leary ME: State-dependent trapping of flecainide in the cardiac sodium channel. J Physiol. 2004 Oct 1;560(Pt 1):37-49. Epub 2004 Jul 22.
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Shimizu W, Antzelevitch C, Suyama K, Kurita T, Taguchi A, Aihara N, Takaki H, Sunagawa K, Kamakura S: Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2000 Dec;11(12):1320-9.
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Liu H, Atkins J, Kass RS: Common molecular determinants of flecainide and lidocaine block of heart Na+ channels: evidence from experiments with neutral and quaternary flecainide analogues. J Gen Physiol. 2003 Mar;121(3):199-214.
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Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
View Article

Sodium channel protein type 4 subunit alpha

Enzymes

Cytochrome P450 2D6

Cytochrome P450 2C9