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Identification
NameFlecainide
Accession NumberDB01195  (APRD00129)
TypeSmall Molecule
GroupsApproved, Withdrawn
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
Synonyms
SynonymLanguageCode
(+-)-FlecainideNot AvailableNot Available
CCRIS 313Not AvailableNot Available
FlecaineNot AvailableNot Available
FlecainidaSpanishINN
FlecainidumLatinINN
N-(2-Piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamideNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tambocortablet100 mgoralValeant Canada Lp Valeant Canada S.E.C.Not AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Tambocortablet50 mgoralValeant Canada Lp Valeant Canada S.E.C.Not AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Flecainide Acetatetablet50 mgoralRoxane Laboratories, Inc.2003-01-14Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet100 mgoralRoxane Laboratories, Inc.2003-01-14Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet150 mgoralRoxane Laboratories, Inc.2003-01-14Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet50 mgoralBarr Laboratories Inc.2002-11-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet100 mgoralBarr Laboratories Inc.2002-11-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet150 mgoralBarr Laboratories Inc.2002-11-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet50 mgoralAv Pak2015-02-09Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet100 mgoralAv Pak2015-02-09Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet150 mgoralAv Pak2015-02-09Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet50 mgoralPhysicians Total Care, Inc.2004-06-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet100 mgoralPhysicians Total Care, Inc.2005-09-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet150 mgoralPhysicians Total Care, Inc.2008-09-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet50 mgoralApotex Corp.2009-07-09Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet100 mgoralApotex Corp.2009-07-09Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet150 mgoralApotex Corp.2009-07-09Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet50 mgoralRanbaxy Pharmaceuticals Inc.2004-02-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet100 mgoralRanbaxy Pharmaceuticals Inc.2004-02-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet150 mgoralRanbaxy Pharmaceuticals Inc.2004-02-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet50 mgoralAmneal Pharmaceuticals of New York, LLC2009-12-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet100 mgoralAmneal Pharmaceuticals of New York, LLC2009-12-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet150 mgoralAmneal Pharmaceuticals of New York, LLC2009-12-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet100 mgoralAmerican Health Packaging2011-07-14Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainide Acetatetablet100 mgoralCarilion Materials Management2003-01-14Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Flecainidetablet50 mgoralAa Pharma IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Flecainidetablet100 mgoralAa Pharma IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Over the Counter ProductsNot Available
International Brands
NameCompany
AlmarytmNot Available
ApocardNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Flecainide acetate
Thumb
  • InChI Key: RKXNZRPQSOPPRN-UHFFFAOYNA-N
  • Monoisotopic Mass: 474.158941118
  • Average Mass: 474.3947
DBSALT000086
Categories
CAS number54143-55-4
WeightAverage: 414.3427
Monoisotopic: 414.137811746
Chemical FormulaC17H20F6N2O3
InChI KeyDJBNUMBKLMJRSA-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)
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as salicylamides. These are carboxamide derivatives of salicylic acid. Salicylic acid is the ortho-hydroxylated derivative of benzoic acid.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentSalicylamides
Alternative Parents
Substituents
  • Salicylamide
  • Benzamide
  • Phenol ether
  • Benzoyl
  • Alkyl aryl ether
  • Piperidine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFlecainide 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.
PharmacodynamicsFlecainide 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 actionFlecainide 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.
AbsorptionNearly complete following oral administration.
Volume of distributionNot Available
Protein binding40%
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).

SubstrateEnzymesProduct
Flecainide
Not Available
Meta-O-dealkylated flecainideDetails
Flecainide
Not Available
Meta-o-dealkylated lactamDetails
Route of eliminationIn 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 life20 hours (range 12-27 hours)
ClearanceNot Available
ToxicityOral 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9856
Blood Brain Barrier+0.8605
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.7773
P-glycoprotein inhibitor IInhibitor0.5307
P-glycoprotein inhibitor IINon-inhibitor0.7716
Renal organic cation transporterNon-inhibitor0.6687
CYP450 2C9 substrateNon-substrate0.8921
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateNon-substrate0.5957
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 substrateNon-inhibitor0.6853
CYP450 2D6 substrateNon-inhibitor0.6556
CYP450 2C19 substrateInhibitor0.5307
CYP450 3A4 substrateNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5538
Ames testNon AMES toxic0.672
CarcinogenicityNon-carcinogens0.8821
BiodegradationNot ready biodegradable0.9968
Rat acute toxicity2.5680 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9409
hERG inhibition (predictor II)Inhibitor0.8474
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral100 mg
Tabletoral150 mg
Tabletoral50 mg
Prices
Unit descriptionCostUnit
Tambocor 150 mg tablet5.75USD tablet
Tambocor 100 mg tablet4.27USD tablet
Flecainide acetate 150 mg tablet3.83USD tablet
Flecainide acetate 100 mg tablet2.95USD tablet
Tambocor 50 mg tablet2.72USD tablet
Flecainide acetate 50 mg tablet1.95USD tablet
Tambocor 100 mg Tablet1.19USD tablet
Apo-Flecainide 100 mg Tablet0.83USD tablet
Tambocor 50 mg Tablet0.6USD tablet
Apo-Flecainide 50 mg Tablet0.41USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point228-229Bmitt, E.H. and Brown, W.R.; U.S. Patent 3,900,481; August 19,1975; assigned to Riker Laboratories, Inc.
water solubility48.4 mg/mL at 37 °C (acetate form)Not Available
logP3.78MANNHOLD,R ET AL. (1990)
pKa9.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0324 mg/mLALOGPS
logP2.98ALOGPS
logP3.19ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)13.68ChemAxon
pKa (Strongest Basic)9.62ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area59.59 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity88.4 m3·mol-1ChemAxon
Polarizability35.92 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraMS
References
Synthesis Reference

Bmitt, E.H. and Brown, W.R.; U.S. Patent 3,900,481; August 19,1975; assigned to Riker Laboratories, Inc.

US3900481A
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
ATC CodesC01BC04
AHFS Codes
  • 24:04.04.12
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (77.1 KB)
Interactions
Drug Interactions
Drug
AcetazolamideCarbonic Anhydrase Inhibitors may increase the serum concentration of Flecainide.
AmiodaroneAmiodarone may enhance the QTc-prolonging effect of Flecainide. Amiodarone may increase the serum concentration of Flecainide.
AripiprazoleCYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole.
BoceprevirMay increase the serum concentration of Flecainide.
DarunavirMay increase the serum concentration of CYP2D6 Substrates.
DiclofenamideMay increase the serum concentration of Flecainide. Exceptions: Brinzolamide; Dorzolamide.
DigoxinMay increase the serum concentration of Digoxin.
EthoxzolamideMay increase the serum concentration of Flecainide. Exceptions: Brinzolamide; Dorzolamide.
EtravirineMay decrease the serum concentration of Flecainide.
FosamprenavirMay increase the serum concentration of Flecainide.
LopinavirRitonavir may increase the serum concentration of Flecainide.
MethazolamideCarbonic Anhydrase Inhibitors may increase the serum concentration of Flecainide.
MifepristoneMay enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents.
MirabegronMay increase the serum concentration of Flecainide.
PanobinostatMay increase the serum concentration of CYP2D6 Substrates.
Peginterferon alfa-2bMay decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates.
RitonavirRitonavir may increase the serum concentration of Flecainide.
SaquinavirMay enhance the arrhythmogenic effect of Flecainide. Saquinavir may increase the serum concentration of Flecainide.
Sodium bicarbonateMay diminish the arrhythmogenic effect of Flecainide. Sodium Bicarbonate may increase the serum concentration of Flecainide.
TelaprevirMay enhance the adverse/toxic effect of Flecainide.
TipranavirTipranavir may increase the serum concentration of Flecainide.
TopiramateCarbonic Anhydrase Inhibitors may increase the serum concentration of Flecainide.
VerapamilMay enhance the adverse/toxic effect of Flecainide. In particular, this combination may significantly impair myocardial contractility and AV nodal conduction.
ZonisamideCarbonic Anhydrase Inhibitors may increase the serum concentration of Flecainide.
Food Interactions
  • Take without regard to meals.

Targets

1. Sodium channel protein type 5 subunit alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium channel protein type 5 subunit alpha Q14524 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium channel protein type 4 subunit alpha P35499 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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
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Drug created on June 13, 2005 07:24 / Updated on April 22, 2014 15:34