Identification

Name
Flecainide
Accession Number
DB01195  (APRD00129)
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Flecainide is a Class I anti-arrhythmic agent like encainide and propafenone.7 Flecainide’s development began in 1966 and was first synthesized in 1972 as an attempt to generate new anesthetics.10 It is used to prevent supraventricular and ventricular arrhythmias, as well as paroxysmal atrial fibrillation and flutter.12,13

Flecainide was granted FDA approval on 31 October 1985.11

Structure
Thumb
Synonyms
  • (±)-flecainide
  • Flecaine
  • Flecainida
  • Flécaïnide
  • Flecainide
  • Flecainidum
  • N-(2-Piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide
External IDs
CCRIS 313
Product Ingredients
IngredientUNIICASInChI Key
Flecainide acetateM8U465Q1WQ54143-56-5RKXNZRPQSOPPRN-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Flecainide AcetateTablet100 mg/1OralMylan Pharmaceuticals2011-08-022012-03-31Us
Flecainide AcetateTablet50 mg/1OralMylan Pharmaceuticals2011-08-022011-11-30Us
Flecainide acetateTablet150 mg/1OralCounty Line Pharmaceuticals, LLC2016-11-042019-10-01Us
Flecainide acetateTablet100 mg/1OralCounty Line Pharmaceuticals, LLC2016-11-042019-10-01Us
Flecainide acetateTablet50 mg/1OralCounty Line Pharmaceuticals, LLC2016-11-042019-10-01Us
Flecainide AcetateTablet150 mg/1OralMylan Pharmaceuticals2011-08-022011-11-30Us
TambocorTablet100 mg/1OralGraceway Pharmaceuticals2007-04-012013-04-30Us
TambocorTablet50 mg/1OralGraceway Pharmaceuticals2007-04-012013-04-30Us
TambocorTablet150 mg/1OralMedicis Pharmaceutical Corporation2011-11-282013-04-30Us
TambocorTablet100 mg/1OralMedicis Pharmaceutical Corporation2011-11-282013-04-30Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-flecainideTabletOralApotex Corporation2006-05-08Not applicableCanada
Apo-flecainideTabletOralApotex Corporation2006-05-08Not applicableCanada
Auro-flecainideTabletOralAuro Pharma Inc2017-02-27Not applicableCanada
Auro-flecainideTabletOralAuro Pharma Inc2017-02-27Not applicableCanada
Flecainide AcetateTablet50 mg/1OralAmerincan Health Packaging2016-07-182019-05-31Us
Flecainide AcetateTablet100 mg/1OralPhysicians Total Care, Inc.2005-09-02Not applicableUs54868 540520180907 15195 1lw0keq
Flecainide AcetateTablet150 mg/1OralANI Pharmaceuticals, Inc.2015-12-28Not applicableUs
Flecainide AcetateTablet100 mg/1OralBarr Laboratories2002-11-192017-07-31Us00555 0860 02 nlmimage10 d72f6beb
Flecainide AcetateTablet50 mg/1Oralbryant ranch prepack2015-07-08Not applicableUs
Flecainide AcetateTablet50 mg/1OralBarr Laboratories2002-11-182017-07-31Us00555 0859 02 nlmimage10 512f2899
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Almarytm / Apocard
Categories
UNII
K94FTS1806
CAS number
54143-55-4
Weight
Average: 414.3427
Monoisotopic: 414.137811746
Chemical Formula
C17H20F6N2O3
InChI Key
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)
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

Pharmacology

Indication

In New Zealand and America, flecainide is indicated to prevent supraventricular arrhythmias and ventricular arrhythmias.12 In the United States, it is also indicated to prevent paroxysmal atrial fibrillation and flutter.9,13

Associated Conditions
Pharmacodynamics

Flecainide inhibits the action of sodium and potassium ion channels in the heart, raising the threshold for depolarization and correcting arrhythmias.10 Flecainide has a long duration of action, allowing for once daily dosing.12 The therapeutic index is narrow.8 Patients should not take this medication if there is already structural heart disease or left ventricular systolic dysfunction.12

Mechanism of action

Flecainide blocks fast inward sodium channels and slowly unbinds during diastole, prolonging the refractory period of the heart.10 This blockade also shortens the duration of action potentials through the Purkinjie fibers.10 Flecainide also prevents delayed rectifier potassium channels from opening, lengthening the action potential through ventricular and atrial muscle fibers.10 Finally, flecainide also blocks ryanodine receptor opening, reducing calcium release from sarcoplasmic reticulum, which reduces depolarization of cells.10

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Humans
ASodium channel protein type 4 subunit alpha
inhibitor
Humans
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Humans
URyanodine receptor 2
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Oral flecainide has a Tmax of 3-4h and a bioavialability of 90%.6,10 Taking flecainide with food or aluminum hydroxide antacids do not significantly affect the absorption of flecainide.6,12,13

Volume of distribution

The average volume of distribution in 8 male subjects is 5.0-13.4L/kg.6

Protein binding

Flecainide is 40% bound to protein in serum, mainly to alpha-1-acid glycoprotein and minorly to serum albumin.6,13

Metabolism

Flecainide is mainly metabolized to meta-O-dealkylated flecainide or the meta-O-dealkylated lactam of flecainide.6 Meta-O-dealkylated flecainide has 20% the activity of flecainide.6 Both of these metabolites are generally detected as glucuronide or sulfate conjugates.6 Flecainide’s metabolism involves the action of CYP2D6 and CYP1A2.13,10

Route of elimination

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.6,12,13 5% is eliminated in the feces.6,13

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.6,12,13 In patients with a ventricular premature complex, flecainide has a half life of 20 hours.6,13 The half life of meta-O-dealkylated flecainide, a major metabolite of flecainide, is 12.6h.6

Clearance

The average clearance of intravenous flecainide is 4.6-12.1mL/min/kg in 8 male subjects.6 For oral flecainide, the clearance was 4-20mL/min/kg.6

Toxicity

The oral LD50 in rats is 1346mg/kg and in mice is 170mg/kg.14 The subcutaneous LD50 in rats is 215mg/kg and in mice is 188mg/kg.14 The oral TDLO in women is 20mg/kg and in men is 40mg/kg/2W.14

Patients experiencing an overdose may present with ECG abnormalities such as a lengthened PR interval, increased QRS duration, prolonged QT interval, increased amplitude of the T wave, reduced myocardial rate and contractility, hypotension, or death.12,13 Treat patients with symptomatic and supportive treatment which may involve administration of inotropic agents, assisted respiration, circulatory assistance, and acidification of the urine.12,13 Hemodialysis is not expected to be useful in the removal of flecainide from serum.6,13

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Flecainide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Flecainide.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Flecainide.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Flecainide can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
4-MethoxyamphetamineThe metabolism of Flecainide can be decreased when combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Flecainide.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Flecainide.
8-azaguanineThe metabolism of 8-azaguanine can be decreased when combined with Flecainide.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be decreased when combined with Flecainide.
9-DeazaguanineThe metabolism of 9-Deazaguanine can be decreased when combined with Flecainide.
9-MethylguanineThe metabolism of 9-Methylguanine can be decreased when combined with Flecainide.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
  • Take with or without food. The absorption is unaffected by food.

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 References
  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:1449923]
  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:2115193]
  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:1900101]
  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:8541168]
  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:12687841]
  6. Conard GJ, Ober RE: Metabolism of flecainide. Am J Cardiol. 1984 Feb 27;53(5):41B-51B. doi: 10.1016/0002-9149(84)90501-0. [PubMed:6364769]
  7. Abi Samra F: The clinical use of class IC antiarrhythmic drugs. J La State Med Soc. 1989 May;141(5):27-31. [PubMed:2499646]
  8. Tamargo J, Le Heuzey JY, Mabo P: Narrow therapeutic index drugs: a clinical pharmacological consideration to flecainide. Eur J Clin Pharmacol. 2015 May;71(5):549-67. doi: 10.1007/s00228-015-1832-0. Epub 2015 Apr 15. [PubMed:25870032]
  9. Aliot E, Capucci A, Crijns HJ, Goette A, Tamargo J: Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation. Europace. 2011 Feb;13(2):161-73. doi: 10.1093/europace/euq382. Epub 2010 Dec 7. [PubMed:21138930]
  10. Andrikopoulos GK, Pastromas S, Tzeis S: Flecainide: Current status and perspectives in arrhythmia management. World J Cardiol. 2015 Feb 26;7(2):76-85. doi: 10.4330/wjc.v7.i2.76. [PubMed:25717355]
  11. FDA Approved Drug Products: Tambocor Flecainide Acetate Oral Tablets [Link]
  12. Medsafe New Zealand Approved Drug Products: Tambocor Oral Tablets and Capsules [Link]
  13. Flecainide Acetate [Link]
  14. Cayman Chemicals: Flecainide MSDS [Link]
External Links
Human Metabolome Database
HMDB0015326
KEGG Drug
D07962
KEGG Compound
C07001
PubChem Compound
3356
PubChem Substance
46508078
ChemSpider
3239
BindingDB
50131434
RxNav
4441
ChEBI
75984
ChEMBL
CHEMBL652
Therapeutic Targets Database
DAP000518
PharmGKB
PA449646
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Flecainide
ATC Codes
C01BC04 — Flecainide
AHFS Codes
  • 24:04.04.12 — Class IC Antiarrythmics
MSDS
Download (77.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedSupportive CarePain1
2CompletedTreatmentArrhythmia / Arrhythmia of ventricular origin / Cardiovascular Heart Disease / Heart Diseases1
2CompletedTreatmentFailed First Radiofrequency Ablation Procedure / Paroxysmal Atrial Fibrillation (PAF)1
2CompletedTreatmentNarcolepsy1
2RecruitingTreatmentArrhythmogenic Right Ventricular Cardiomyopathy (ARVC)1
2RecruitingTreatmentParoxysmal Atrial Fibrillation (PAF)1
2TerminatedBasic ScienceBlood Pressures / Ventricular Premature Complexes1
2, 3WithdrawnTreatmentAtrial Fibrillation (AF) / Recurrences1
3CompletedPreventionArrhythmia of ventricular origin / Cardiovascular Heart Disease / Coronary Heart Disease (CHD) / Death, Sudden,Cardiac / Heart Arrest / Heart Diseases / Myocardial Infarction / Myocardial Ischemia1
3CompletedTreatmentArrhythmia / Atrial Fibrillation (AF) / Cardiovascular Heart Disease / Heart Diseases1
3CompletedTreatmentParoxysmal Atrial Fibrillation (PAF)1
3RecruitingTreatmentFetal Atrial Flutter Without Hydrops / Fetal Supraventricular Tachycardia With Hydrops / Fetal Supraventricular Tachycardia Without Hydrops1
3SuspendedTreatmentAtrial Fibrillation (AF)1
4CompletedNot AvailableParoxysmal Atrial Fibrillation (PAF)1
4CompletedTreatmentAtrial Fibrillation (AF)2
4CompletedTreatmentAtrial Fibrillation (AF) / Brugada Syndrome / Ventricular Tachycardia (VT)1
4RecruitingTreatmentAtrial Fibrillation (AF)2
4RecruitingTreatmentCarvedilol / Outflow Tract / Ventricular Premature Complexes1
4RecruitingTreatmentParoxysmal Atrial Fibrillation (PAF)1
4TerminatedTreatmentAtrial Fibrillation (AF)1
4Unknown StatusNot AvailableVentricular Premature Complexes / Ventricular Tachycardia (VT)1
4Unknown StatusDiagnosticAtrial Fibrillation (AF)1
4WithdrawnTreatmentAtrial Fibrillation (AF)1
Not AvailableActive Not RecruitingTreatmentAtrial Fibrillation (AF)1
Not AvailableActive Not RecruitingTreatmentAtrial Fibrillation (AF) / Quality of Life1
Not AvailableCompletedNot AvailableArrhythmogenic Right Ventricular Cardiomyopathy (ARVC) / Brugada Syndrome1
Not AvailableCompletedTreatmentAtrial Fibrillation (AF)3
Not AvailableCompletedTreatmentCatecholaminergic Polymorphic Ventricular Tachycardia (CPVT)1
Not AvailableCompletedTreatmentHeart Failure / Recurrent Atrial Fibrillation1
Not AvailableNot Yet RecruitingNot AvailableTachycardia, Supraventricular1
Not AvailableRecruitingTreatmentVentricular premature beats1
Not AvailableUnknown StatusTreatmentParoxysmal Atrial Fibrillation (PAF)1
Not AvailableUnknown StatusTreatmentPersistent Atrial Fibrillation1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • 3M Health Care
  • Alphapharm Party Ltd.
  • Amneal Pharmaceuticals
  • AQ Pharmaceuticals Inc.
  • Barr Pharmaceuticals
  • Graceway Pharmaceuticals
  • Kaiser Foundation Hospital
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Ohm Laboratories Inc.
  • Par Pharmaceuticals
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Ranbaxy Laboratories
  • Roxane Labs
  • Southwood Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral
TabletOral100 mg/1
TabletOral150 mg/1
TabletOral50 mg/1
TabletOral100 mg
TabletOral100000 ug/1
TabletOral150000 ug/1
TabletOral50 mg
TabletOral50000 ug/1
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)228-229Bmitt, 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)FDA Label
logP3.78MANNHOLD,R ET AL. (1990)
pKa9.3FDA Label
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.6853
CYP450 2D6 inhibitorNon-inhibitor0.6556
CYP450 2C19 inhibitorInhibitor0.5307
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-001i-9000000000-b732167df77d39193144
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00dl-0095000000-644485d209c90776a32d
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0190000000-201f2152d161a1ff83e5
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0790000000-928874c4b348381ad1b8
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0596-0940000000-ee7a94ba0d7bcfa2fe93
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-052g-1910000000-a32ac2f605f11fbbc5e0
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0297-1900000000-f1c49d25a6b161ff44d9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0000900000-9820e909cb01d45fa815
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kb-2009500000-68b872fada8afdd4e580
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0f6t-5019000000-8fa5e4257c88beda0ea1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0uea-8069000000-149a79cf429446ec77c2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0uei-6292000000-103ccdef98c4b6c9e408
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0pdi-8970000000-9258d139b203d6c98df0

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzamides. These are organic compounds containing a carboxamido substituent attached to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Benzamides
Alternative Parents
Phenoxy compounds / Phenol ethers / Benzoyl derivatives / Alkyl aryl ethers / Piperidines / Secondary carboxylic acid amides / Amino acids and derivatives / Dialkylamines / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
Benzamide / Phenoxy compound / Benzoyl / Phenol ether / Alkyl aryl ether / Piperidine / Amino acid or derivatives / Carboxamide group / Secondary carboxylic acid amide / Carboxylic acid derivative
show 18 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, organofluorine compound, aromatic ether, monocarboxylic acid amide (CHEBI:75984)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
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 pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. 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. [PubMed:10617684]
  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:10758053]
  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:10961955]
  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:11307783]
  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:11535580]
  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:15272045]
  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:11196553]
  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:12601084]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity
Specific Function
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 pr...
Gene Name
SCN4A
Uniprot ID
P35499
Uniprot Name
Sodium channel protein type 4 subunit alpha
Molecular Weight
208059.175 Da
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:14608015]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [PubMed:15272206]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Suramin binding
Specific Function
Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activa...
Gene Name
RYR2
Uniprot ID
Q92736
Uniprot Name
Ryanodine receptor 2
Molecular Weight
564562.71 Da
References
  1. Mehra D, Imtiaz MS, van Helden DF, Knollmann BC, Laver DR: Multiple modes of ryanodine receptor 2 inhibition by flecainide. Mol Pharmacol. 2014 Dec;86(6):696-706. doi: 10.1124/mol.114.094623. Epub 2014 Oct 1. [PubMed:25274603]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Doki K, Homma M, Kuga K, Aonuma K, Kohda Y: Effects of CYP2D6 genotypes on age-related change of flecainide metabolism: involvement of CYP1A2-mediated metabolism. Br J Clin Pharmacol. 2009 Jul;68(1):89-96. doi: 10.1111/j.1365-2125.2009.03435.x. [PubMed:19660006]
  2. Lim KS, Jang IJ, Kim BH, Kim J, Jeon JY, Tae YM, Yi S, Eum S, Cho JY, Shin SG, Yu KS: Changes in the QTc interval after administration of flecainide acetate, with and without coadministered paroxetine, in relation to cytochrome P450 2D6 genotype: data from an open-label, two-period, single-sequence crossover study in healthy Korean male subjects. Clin Ther. 2010 Apr;32(4):659-66. doi: 10.1016/j.clinthera.2010.04.002. [PubMed:20435235]
  3. Walker DK, Alabaster CT, Congrave GS, Hargreaves MB, Hyland R, Jones BC, Reed LJ, Smith DA: Significance of metabolism in the disposition and action of the antidysrhythmic drug, dofetilide. In vitro studies and correlation with in vivo data. Drug Metab Dispos. 1996 Apr;24(4):447-55. [PubMed:8801060]
  4. Andrikopoulos GK, Pastromas S, Tzeis S: Flecainide: Current status and perspectives in arrhythmia management. World J Cardiol. 2015 Feb 26;7(2):76-85. doi: 10.4330/wjc.v7.i2.76. [PubMed:25717355]
  5. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Andrikopoulos GK, Pastromas S, Tzeis S: Flecainide: Current status and perspectives in arrhythmia management. World J Cardiol. 2015 Feb 26;7(2):76-85. doi: 10.4330/wjc.v7.i2.76. [PubMed:25717355]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Enzyme inhibition data based on findings of 1 in vitro study.
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Walker DK, Alabaster CT, Congrave GS, Hargreaves MB, Hyland R, Jones BC, Reed LJ, Smith DA: Significance of metabolism in the disposition and action of the antidysrhythmic drug, dofetilide. In vitro studies and correlation with in vivo data. Drug Metab Dispos. 1996 Apr;24(4):447-55. [PubMed:8801060]

Carriers

Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...

Components:
References
  1. Conard GJ, Ober RE: Metabolism of flecainide. Am J Cardiol. 1984 Feb 27;53(5):41B-51B. doi: 10.1016/0002-9149(84)90501-0. [PubMed:6364769]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Conard GJ, Ober RE: Metabolism of flecainide. Am J Cardiol. 1984 Feb 27;53(5):41B-51B. doi: 10.1016/0002-9149(84)90501-0. [PubMed:6364769]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Doki K, Apati S, Sakata T, Homma M: Involvement of Renal Efflux Transporter MATE1 in Renal Excretion of Flecainide. Biol Pharm Bull. 2019;42(7):1226-1229. doi: 10.1248/bpb.b19-00031. [PubMed:31257298]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Doki K, Apati S, Sakata T, Homma M: Involvement of Renal Efflux Transporter MATE1 in Renal Excretion of Flecainide. Biol Pharm Bull. 2019;42(7):1226-1229. doi: 10.1248/bpb.b19-00031. [PubMed:31257298]

Drug created on June 13, 2005 07:24 / Updated on March 27, 2020 16:58

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