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Identification
Name Flecainide
Accession Number DB01195 (APRD00129)
Type small molecule
Groups approved
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. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Flecainida [INN-Spanish]
Flecainidum [INN-Latin]
Salts
  • Flecainide acetate
Brand names
Name Company
Almarytm
Apocard
Ecrinal
Flécaine
Tambocor 3M pharmaceuticals
Brand mixtures Not Available
Categories
  • Antiarrhythmic Agents
  • Anti-Arrhythmia Agents
CAS number 54143-55-4
Weight Average: 414.3427
Monoisotopic: 414.137811746
Chemical Formula C17H20F6N2O3
InChI Key InChIKey=DJBNUMBKLMJRSA-UHFFFAOYSA-N
InChI
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)
Plain Text
IUPAC Name
N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide
SMILES
FC(F)(F)COC1=CC(C(=O)NCC2CCCCN2)=C(OCC(F)(F)F)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenols and Derivatives
  • Ethers
  • Hydroquinones
  • Anisoles
  • Benzoyl Derivatives
  • Benzamides
Substructures
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Amino Ketones
  • Ethers
  • Halogen Derivatives
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Hydroquinones
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Benzoyl Derivatives
  • Phenyl Esters
  • Benzamides
  • Piperidines
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.
Pharmacodynamics 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 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.
Absorption Nearly complete following oral administration.
Volume of distribution Not Available
Protein binding 40%
Metabolism 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)
Clearance Not Available
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
Pathways
Pathway Name SMPDB ID
Smp00331 Flecainide Pathway SMP00331
Pharmacoeconomics
Manufacturers
  • Amneal pharmaceutical
  • Apotex inc
  • Barr laboratories inc
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Graceway pharmaceuticals llc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Tambocor 150 mg tablet 5.75 USD tablet
Tambocor 100 mg tablet 4.27 USD tablet
Flecainide acetate 150 mg tablet 3.83 USD tablet
Flecainide acetate 100 mg tablet 2.95 USD tablet
Tambocor 50 mg tablet 2.72 USD tablet
Flecainide acetate 50 mg tablet 1.95 USD tablet
Tambocor 100 mg Tablet 1.19 USD tablet
Apo-Flecainide 100 mg Tablet 0.83 USD tablet
Tambocor 50 mg Tablet 0.6 USD tablet
Apo-Flecainide 50 mg Tablet 0.41 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 145-147 °C PhysProp
water solubility 48.4 mg/mL at 37 °C (acetate form) Not Available
logP 3.78 MANNHOLD,R ET AL. (1990)
pKa 9.3 Not Available
Predicted Properties
Property Value Source
water solubility 3.24e-02 g/l ALOGPS
logP 2.98 ALOGPS
logP 3.19 ChemAxon
logS -4.1 ALOGPS
pKa (strongest acidic) 13.68 ChemAxon
pKa (strongest basic) 9.62 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 59.59 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 88.4 ChemAxon
polarizability 35.92 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Gill JS, Mehta D, Ward DE, Camm AJ: Efficacy of flecainide, sotalol, and verapamil in the treatment of right ventricular tachycardia in patients without overt cardiac abnormality. Br Heart J. 1992 Oct;68(4):392-7. Pubmed
  2. Sakurada H, Hiyoshi Y, Tejima T, Yanase O, Tokuyasu Y, Watanabe K, Motomiya T, Sugiura M, Hiraoka M: [Effects of oral flecainide treatment of refractory tachyarrhythmias] Kokyu To Junkan. 1990 May;38(5):471-6. Pubmed
  3. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL, et al.: Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991 Mar 21;324(12):781-8. Pubmed
  4. Greenberg HM, Dwyer EM Jr, Hochman JS, Steinberg JS, Echt DS, Peters RW: Interaction of ischaemia and encainide/flecainide treatment: a proposed mechanism for the increased mortality in CAST I. Br Heart J. 1995 Dec;74(6):631-5. Pubmed
  5. Gasparini M, Priori SG, Mantica M, Napolitano C, Galimberti P, Ceriotti C, Simonini S: Flecainide test in Brugada syndrome: a reproducible but risky tool. Pacing Clin Electrophysiol. 2003 Jan;26(1 Pt 2):338-41. Pubmed
External Links
Resource Link
KEGG Drug D07962 Link_out
KEGG Compound C07001 Link_out
PubChem Compound 3356 Link_out
PubChem Substance 46508078 Link_out
ChemSpider 3239 Link_out
BindingDB 50131434 Link_out
Therapeutic Targets Database DAP000518 Link_out
PharmGKB PA449646 Link_out
IUPHAR 2560 Link_out
Guide to Pharmacology 2560 Link_out
Drug Product Database 1966197 Link_out
RxList http://www.rxlist.com/cgi/generic2/flecainide.htm Link_out
Drugs.com http://www.drugs.com/cdi/flecainide.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Flecainide Link_out
ATC Codes
  • C01BC04
AHFS Codes
  • 24:04.04.12
PDB Entries Not Available
FDA label Not Available
MSDS show (77.1 KB)
Interactions
Drug Interactions
Drug Interaction
Amiodarone Amiodarone may increase the effect and toxicity of flecainide
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Cimetidine Cimetidine, a moderate CYP2D6 inhibitor, may decrease the metabolism of flecainide.
Cisapride Increased risk of cardiotoxicity and arrhythmias
Duloxetine Possible increase in the levels of this agent when used with duloxetine
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Quinupristin This combination presents an increased risk of toxicity
Ritonavir Ritonavir increases the toxicity of the anti-arrhythmic
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
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.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
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.
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.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
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).
Food Interactions
  • Take without regard to meals.
Targets

1. Sodium channel protein type 5 subunit alpha

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: Q14524 Link_out
Gene: SCN5A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nagatomo T, January CT, Makielski JC: Preferential block of late sodium current in the LQT3 DeltaKPQ mutant by the class I© antiarrhythmic flecainide. Mol Pharmacol. 2000 Jan;57(1):101-7. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed
  6. 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. Pubmed
  7. 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. Pubmed
  8. 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. Pubmed
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Sodium channel protein type 4 subunit alpha

Pharmacological action: yes
Actions: inhibitor

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. This sodium channel may be present in both denervated and innervated skeletal muscle

Organism class: human
UniProt ID: P35499 Link_out
Gene: SCN4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Desaphy JF, De Luca A, Didonna MP, George AL Jr, Camerino Conte D: 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. Epub 2003 Nov 7. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19