Chemical: Drug
flecainide

last updated 02/07/2014

1. DPWG Guideline for flecainide and CYP2D6

Summary

Reduce flecainide dose by 50% for CYP2D6 poor metabolizer (PM) and by 25% for CYP2D6 intermediate metabolizer (IM) patients.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for flecainide based on CYP2D6 genotypes [Article:21412232]. They recommend a lower dose for patients carrying the poor metabolizer (PM) alleles and intermediate metabolizer (IM) alleles.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
PM (two inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) alleles)Reduce dose by 50%, record ECG, monitor plasma concentration.Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Minor clinical effect (S): QTc prolongation (<450 ms female, <470 ms male); INR increase < 4.5; Kinetic effect (S)
IM (two decreased-activity (*9, *10, *17, *29, *36, *41) alleles or carrying one active (*1, *2, *33, *35) and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele, or carrying one decreased-activity (*9, *10, *17, *29, *36, *41) allele and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele)Reduce dose by 25%, record ECG, monitor plasma concentration.Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Minor clinical effect (S): QTc prolongation (<450 ms female, <470 ms male); INR increase < 4.5; Kinetic effect (S)
UM (a gene duplication in absence of inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) or decreased-activity (*9, *10, *17, *29, *36, *41) alleles)Record ECG and monitor plasma concentration or select alternative drug (e.g., sotalol, disopyramide, quinidine, amiodarone).no evidence.--
  • *See Methods or [Article:18253145] for definition of "good" and "moderate" quality.
  • S: statistically significant difference.



PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for flecainide

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA CYP1A2 *1A N/A N/A N/A
No VIP available No VIP available VA CYP1A2 *1F N/A N/A N/A
VIP CA VA CYP2D6 *1 N/A N/A N/A
VIP No VIP available VA CYP2D6 *2 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *3 N/A N/A N/A
VIP CA VA CYP2D6 *4 N/A N/A N/A
No VIP available CA VA CYP2D6 *5 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *6 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *9 N/A N/A N/A
VIP CA VA CYP2D6 *10 N/A N/A N/A
No VIP available CA VA CYP2D6 *14 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *17 N/A N/A N/A
No VIP available CA VA CYP2D6 *21 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *29 N/A N/A N/A
No VIP available CA VA CYP2D6 *36 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *41 N/A N/A N/A
No VIP available No VIP available VA CYP3A5 *1A N/A N/A N/A
No VIP available No VIP available VA CYP3A5 *3A N/A N/A N/A
No VIP available No Clinical Annotations available VA
CYP2D6 extensive metabolizer genotype N/A N/A N/A
VIP No Clinical Annotations available No Variant Annotations available
rs1065852 NC_000022.10:g.42526694G=, NC_000022.10:g.42526694G>A, NC_000022.11:g.42130692G=, NC_000022.11:g.42130692G>A, NG_008376.3:g.4300C=, NG_008376.3:g.4300C>T, NM_000106.5:c.100C=, NM_000106.5:c.100C>T, NM_001025161.2:c.100C=, NM_001025161.2:c.100C>T, NP_000097.3:p.Pro34=, NP_000097.3:p.Pro34Ser, NP_001020332.2:p.Pro34=, NP_001020332.2:p.Pro34Ser, NT_187682.1:g.53033G=, NT_187682.1:g.53033G>A, NW_004504305.1:g.53019A=, NW_004504305.1:g.53019A>G, NW_009646208.1:g.16258A=, NW_009646208.1:g.16258A>G, XM_005278353.1:c.100T=, XM_005278353.1:c.100T>C, XM_005278354.1:c.-1454C>T, XM_005278354.1:c.-1454T>C, XM_005278354.3:c.-1454C>T, XM_005278354.3:c.-1454T>C, XM_011529966.1:c.100C=, XM_011529966.1:c.100C>T, XM_011529967.1:c.100C=, XM_011529967.1:c.100C>T, XM_011529968.1:c.100C=, XM_011529968.1:c.100C>T, XM_011529969.1:c.37+605C>T, XM_011529969.1:c.37+605T>C, XM_011529970.1:c.100C=, XM_011529970.1:c.100C>T, XM_011529971.1:c.37+605C>T, XM_011529971.1:c.37+605T>C, XM_011529972.1:c.100C=, XM_011529972.1:c.100C>T, XM_011547541.1:c.-1454C>T, XM_011547541.1:c.-1454T>C, XM_011547750.1:c.37+605C>T, XM_011547750.1:c.37+605T>C, XM_011547751.1:c.-1114C>T, XM_011547751.1:c.-1114T>C, XM_011547756.1:c.42+469A>G, XM_011547756.1:c.42+469G>A, XM_011548819.1:c.-1454C>T, XM_011548819.1:c.-1454T>C, XP_005278410.1:p.Ser34=, XP_005278410.1:p.Ser34Pro, XP_011528268.1:p.Pro34=, XP_011528268.1:p.Pro34Ser, XP_011528269.1:p.Pro34=, XP_011528269.1:p.Pro34Ser, XP_011528270.1:p.Pro34=, XP_011528270.1:p.Pro34Ser, XP_011528272.1:p.Pro34=, XP_011528272.1:p.Pro34Ser, XP_011528274.1:p.Pro34=, XP_011528274.1:p.Pro34Ser, XR_430455.2:n.328+4A>G, XR_430455.2:n.328+4G>A, XR_952536.1:n.-1751A>G, XR_952536.1:n.-1751G>A, XR_952537.1:n.-1751A>G, XR_952537.1:n.-1751G>A, XR_952538.1:n.-1751A>G, XR_952538.1:n.-1751G>A, XR_952539.1:n.-1462A>G, XR_952539.1:n.-1462G>A, XR_952745.1:n.1257C=, XR_952745.1:n.1257C>T, rs117813846, rs58862176
G > A
SNP
P34S
VIP No Clinical Annotations available No Variant Annotations available
rs16947 NC_000022.10:g.42523943A=, NC_000022.10:g.42523943A>G, NC_000022.11:g.42127941G=, NC_000022.11:g.42127941G>A, NG_008376.3:g.7051C=, NG_008376.3:g.7051C>T, NM_000106.5:c.886C=, NM_000106.5:c.886C>T, NM_001025161.2:c.733C=, NM_001025161.2:c.733C>T, NP_000097.3:p.Arg296=, NP_000097.3:p.Arg296Cys, NP_001020332.2:p.Arg245=, NP_001020332.2:p.Arg245Cys, NT_187682.1:g.50282A=, NT_187682.1:g.50282A>G, NW_004504305.1:g.50268G=, NW_004504305.1:g.50268G>A, NW_009646208.1:g.13507G=, NW_009646208.1:g.13507G>A, XM_005278353.1:c.742C=, XM_005278353.1:c.742C>T, XM_005278354.1:c.586C=, XM_005278354.1:c.586C>T, XM_005278354.3:c.586C=, XM_005278354.3:c.586C>T, XM_011529966.1:c.886C=, XM_011529966.1:c.886C>T, XM_011529967.1:c.886C=, XM_011529967.1:c.886C>T, XM_011529968.1:c.886C=, XM_011529968.1:c.886C>T, XM_011529969.1:c.742C=, XM_011529969.1:c.742C>T, XM_011529970.1:c.733C=, XM_011529970.1:c.733C>T, XM_011529971.1:c.742C=, XM_011529971.1:c.742C>T, XM_011529972.1:c.843+233C>T, XM_011529972.1:c.843+233T>C, XM_011547541.1:c.586C=, XM_011547541.1:c.586C>T, XM_011547750.1:c.742T=, XM_011547750.1:c.742T>C, XM_011547751.1:c.670T=, XM_011547751.1:c.670T>C, XM_011547756.1:c.-2094A>G, XM_011547756.1:c.-2094G>A, XM_011548819.1:c.586C=, XM_011548819.1:c.586C>T, XP_005278410.1:p.Arg248=, XP_005278410.1:p.Arg248Cys, XP_005278411.1:p.Arg196=, XP_005278411.1:p.Arg196Cys, XP_011528268.1:p.Arg296=, XP_011528268.1:p.Arg296Cys, XP_011528269.1:p.Arg296=, XP_011528269.1:p.Arg296Cys, XP_011528270.1:p.Arg296=, XP_011528270.1:p.Arg296Cys, XP_011528271.1:p.Arg248=, XP_011528271.1:p.Arg248Cys, XP_011528272.1:p.Arg245=, XP_011528272.1:p.Arg245Cys, XP_011528273.1:p.Arg248=, XP_011528273.1:p.Arg248Cys, XP_011545843.1:p.Arg196=, XP_011545843.1:p.Arg196Cys, XP_011546052.1:p.Cys248=, XP_011546052.1:p.Cys248Arg, XP_011546053.1:p.Cys224=, XP_011546053.1:p.Cys224Arg, XP_011547121.1:p.Arg196=, XP_011547121.1:p.Arg196Cys, XR_430455.2:n.-1930A>G, XR_430455.2:n.-1930G>A, XR_952745.1:n.2000+233C>T, XR_952745.1:n.2000+233T>C, rs117039205, rs57836231
A > G
SNP
R296C
No VIP available No Clinical Annotations available VA
rs1801253 NC_000010.10:g.115805056G>C, NC_000010.11:g.114045297G>C, NG_012187.1:g.6251G>C, NM_000684.2:c.1165G>C, NP_000675.1:p.Gly389Arg, rs12718339, rs17091259, rs28365052, rs59130083
G > C
SNP
G389R
VIP No Clinical Annotations available No Variant Annotations available
rs28371706 NC_000022.10:g.42525772G>A, NC_000022.11:g.42129770G>A, NG_008376.3:g.5222C>T, NM_000106.5:c.320C>T, NM_001025161.2:c.320C>T, NP_000097.3:p.Thr107Ile, NP_001020332.2:p.Thr107Ile, NT_187682.1:g.52111G>A, NW_004504305.1:g.52097G>A, NW_009646208.1:g.15336G>A, XM_005278353.1:c.320C>T, XM_005278354.1:c.-532C>T, XM_005278354.3:c.-532C>T, XM_011529966.1:c.320C>T, XM_011529967.1:c.320C>T, XM_011529968.1:c.320C>T, XM_011529969.1:c.177C>T, XM_011529970.1:c.320C>T, XM_011529971.1:c.177C>T, XM_011529972.1:c.320C>T, XM_011547541.1:c.-532C>T, XM_011547750.1:c.177C>T, XM_011547751.1:c.-192C>T, XM_011547756.1:c.-265G>A, XM_011548819.1:c.-532C>T, XP_005278410.1:p.Thr107Ile, XP_011528268.1:p.Thr107Ile, XP_011528269.1:p.Thr107Ile, XP_011528270.1:p.Thr107Ile, XP_011528271.1:p.His59=, XP_011528272.1:p.Thr107Ile, XP_011528273.1:p.His59=, XP_011528274.1:p.Thr107Ile, XP_011546052.1:p.His59=, XR_430455.2:n.-101G>A, XR_952745.1:n.1477C>T, rs587777915, rs59604033
G > A
SNP
T107I
VIP No Clinical Annotations available No Variant Annotations available
rs28371725 NC_000022.10:g.42523805C>T, NC_000022.11:g.42127803C>T, NG_008376.3:g.7189G>A, NM_000106.5:c.985+39G>A, NM_001025161.2:c.832+39G>A, NT_187682.1:g.50144C>T, NW_004504305.1:g.50130C>T, NW_009646208.1:g.13369C>T, XM_005278353.1:c.841+39G>A, XM_005278354.1:c.685+39G>A, XM_005278354.3:c.685+39G>A, XM_011529966.1:c.985+39G>A, XM_011529967.1:c.985+39G>A, XM_011529968.1:c.985+39G>A, XM_011529969.1:c.841+39G>A, XM_011529970.1:c.832+39G>A, XM_011529971.1:c.841+39G>A, XM_011529972.1:c.844-169G>A, XM_011547541.1:c.724G>A, XM_011547750.1:c.841+39G>A, XM_011547751.1:c.769+39G>A, XM_011548819.1:c.724G>A, XP_011545843.1:p.Glu242Lys, XP_011547121.1:p.Glu242Lys, XR_952745.1:n.2001-169G>A, rs57124011, rs587777916
C > T
SNP
VIP No Clinical Annotations available No Variant Annotations available
rs35742686 NC_000022.10:g.42524244delT, NC_000022.11:g.42128242delT, NG_008376.3:g.6750delA, NM_000106.5:c.775delA, NM_001025161.2:c.622delA, NP_000097.3:p.Arg259Glyfs, NP_001020332.2:p.Arg208Glyfs, NT_187682.1:g.50583delT, NW_004504305.1:g.50569delT, NW_009646208.1:g.13808delT, XM_005278353.1:c.631delA, XM_005278354.1:c.475delA, XM_005278354.3:c.475delA, XM_011529966.1:c.775delA, XM_011529967.1:c.775delA, XM_011529968.1:c.775delA, XM_011529969.1:c.631delA, XM_011529970.1:c.622delA, XM_011529971.1:c.631delA, XM_011529972.1:c.775delA, XM_011547541.1:c.475delA, XM_011547750.1:c.631delA, XM_011547751.1:c.559delA, XM_011547756.1:c.-1793delT, XM_011548819.1:c.475delA, XP_005278410.1:p.Arg211Glyfs, XP_005278411.1:p.Arg159Glyfs, XP_011528268.1:p.Arg259Glyfs, XP_011528269.1:p.Arg259Glyfs, XP_011528270.1:p.Arg259Glyfs, XP_011528271.1:p.Arg211Glyfs, XP_011528272.1:p.Arg208Glyfs, XP_011528273.1:p.Arg211Glyfs, XP_011528274.1:p.Arg259Glyfs, XP_011545843.1:p.Arg159Glyfs, XP_011546052.1:p.Arg211Glyfs, XP_011546053.1:p.Arg187Glyfs, XP_011547121.1:p.Arg159Glyfs, XR_430455.2:n.-1629delT, XR_952745.1:n.1932delA, rs45593132, rs60790764
T > -
T > T
indel
R259G
VIP No Clinical Annotations available No Variant Annotations available
rs3892097 NC_000022.10:g.42524947C=, NC_000022.10:g.42524947C>T, NC_000022.11:g.42128945C=, NC_000022.11:g.42128945C>T, NG_008376.3:g.6047G=, NG_008376.3:g.6047G>A, NM_000106.5:c.506-1A>G, NM_000106.5:c.506-1G>A, NM_001025161.2:c.353-1A>G, NM_001025161.2:c.353-1G>A, NT_187682.1:g.51286C=, NT_187682.1:g.51286C>T, NW_004504305.1:g.51272T=, NW_004504305.1:g.51272T>C, NW_009646208.1:g.14511C=, NW_009646208.1:g.14511C>T, XM_005278353.1:c.363-2A>G, XM_005278353.1:c.363-2G>A, XM_005278354.1:c.207-2A>G, XM_005278354.1:c.207-2G>A, XM_005278354.3:c.207-2A>G, XM_005278354.3:c.207-2G>A, XM_011529966.1:c.506-1A>G, XM_011529966.1:c.506-1G>A, XM_011529967.1:c.506-1A>G, XM_011529967.1:c.506-1G>A, XM_011529968.1:c.506-1A>G, XM_011529968.1:c.506-1G>A, XM_011529969.1:c.363-2A>G, XM_011529969.1:c.363-2G>A, XM_011529970.1:c.353-1A>G, XM_011529970.1:c.353-1G>A, XM_011529971.1:c.363-2A>G, XM_011529971.1:c.363-2G>A, XM_011529972.1:c.506-1A>G, XM_011529972.1:c.506-1G>A, XM_011547541.1:c.207-2A>G, XM_011547541.1:c.207-2G>A, XM_011547750.1:c.363-2A>G, XM_011547750.1:c.363-2G>A, XM_011547751.1:c.290-1A>G, XM_011547751.1:c.290-1G>A, XM_011547756.1:c.-1090C>T, XM_011547756.1:c.-1090T>C, XM_011548819.1:c.207-2A>G, XM_011548819.1:c.207-2G>A, XR_430455.2:n.-926C>T, XR_430455.2:n.-926T>C, XR_952745.1:n.1663-1A>G, XR_952745.1:n.1663-1G>A, rs1800716, rs28371711, rs60082401, rs606231227
C > T
SNP
VIP No Clinical Annotations available No Variant Annotations available
rs5030655 NC_000022.10:g.42525086delA, NC_000022.11:g.42129084delA, NG_008376.3:g.5908delT, NM_000106.5:c.454delT, NM_001025161.2:c.353-140delT, NP_000097.3:p.Trp152Glyfs, NT_187682.1:g.51425delA, NW_004504305.1:g.51411delA, NW_009646208.1:g.14650delA, XM_005278353.1:c.363-141delT, XM_005278354.1:c.155delT, XM_005278354.3:c.155delT, XM_011529966.1:c.454delT, XM_011529967.1:c.454delT, XM_011529968.1:c.454delT, XM_011529969.1:c.311delT, XM_011529970.1:c.353-140delT, XM_011529971.1:c.311delT, XM_011529972.1:c.454delT, XM_011547541.1:c.155delT, XM_011547750.1:c.311delT, XM_011547751.1:c.238delT, XM_011547756.1:c.-951delA, XM_011548819.1:c.155delT, XP_005278411.1:p.Val52Glyfs, XP_011528268.1:p.Trp152Glyfs, XP_011528269.1:p.Trp152Glyfs, XP_011528270.1:p.Trp152Glyfs, XP_011528271.1:p.Val104Glyfs, XP_011528273.1:p.Val104Glyfs, XP_011528274.1:p.Trp152Glyfs, XP_011545843.1:p.Val52Glyfs, XP_011546052.1:p.Val104Glyfs, XP_011546053.1:p.Trp80Glyfs, XP_011547121.1:p.Val52Glyfs, XR_430455.2:n.-787delA, XR_952745.1:n.1611delT, rs11568727, rs28371709
A > -
A > A
indel
W152G
VIP No Clinical Annotations available No Variant Annotations available
rs5030656 NC_000022.10:g.42524176_42524178delCTT, NC_000022.11:g.42128174_42128176delCTT, NG_008376.3:g.6816_6818delAAG, NM_000106.5:c.841_843delAAG, NM_001025161.2:c.688_690delAAG, NP_000097.3:p.Lys281del, NP_001020332.2:p.Lys230del, NT_187682.1:g.50515_50517delCTT, NW_004504305.1:g.50501_50503delCTT, NW_009646208.1:g.13740_13742delCTT, XM_005278353.1:c.697_699delAAG, XM_005278354.1:c.541_543delAAG, XM_005278354.3:c.541_543delAAG, XM_011529966.1:c.841_843delAAG, XM_011529967.1:c.841_843delAAG, XM_011529968.1:c.841_843delAAG, XM_011529969.1:c.697_699delAAG, XM_011529970.1:c.688_690delAAG, XM_011529971.1:c.697_699delAAG, XM_011529972.1:c.841_843delAAG, XM_011547541.1:c.541_543delAAG, XM_011547750.1:c.697_699delAAG, XM_011547751.1:c.625_627delAAG, XM_011547756.1:c.-1861_-1859del, XM_011548819.1:c.541_543delAAG, XP_005278410.1:p.Lys233del, XP_005278411.1:p.Lys181del, XP_011528268.1:p.Lys281del, XP_011528269.1:p.Lys281del, XP_011528270.1:p.Lys281del, XP_011528271.1:p.Lys233del, XP_011528272.1:p.Lys230del, XP_011528273.1:p.Lys233del, XP_011528274.1:p.Lys281del, XP_011545843.1:p.Lys181del, XP_011546052.1:p.Lys233del, XP_011546053.1:p.Lys209del, XP_011547121.1:p.Lys181del, XR_430455.2:n.-1697_-1695del, XR_952745.1:n.1998_2000delAAG, rs587777919
CTT > -
CTT > CTT
indel
VIP No Clinical Annotations available No Variant Annotations available
rs59421388 NC_000022.10:g.42523610C>T, NC_000022.11:g.42127608C>T, NG_008376.3:g.7384G>A, NM_000106.5:c.1012G>A, NM_001025161.2:c.859G>A, NP_000097.3:p.Val338Met, NP_001020332.2:p.Val287Met, NT_187682.1:g.49949C>T, NW_004504305.1:g.49935C>T, NW_009646208.1:g.13174C>T, XM_005278353.1:c.868G>A, XM_005278354.1:c.712G>A, XM_005278354.3:c.712G>A, XM_011529966.1:c.1012G>A, XM_011529967.1:c.1012G>A, XM_011529968.1:c.1012G>A, XM_011529969.1:c.868G>A, XM_011529970.1:c.859G>A, XM_011529971.1:c.868G>A, XM_011529972.1:c.870G>A, XM_011547541.1:c.*118G>A, XM_011547750.1:c.868G>A, XM_011547751.1:c.796G>A, XM_011548819.1:c.*118G>A, XP_005278410.1:p.Val290Met, XP_005278411.1:p.Val238Met, XP_011528268.1:p.Val338Met, XP_011528269.1:p.Val338Met, XP_011528270.1:p.Val338Met, XP_011528271.1:p.Val290Met, XP_011528272.1:p.Val287Met, XP_011528273.1:p.Val290Met, XP_011528274.1:p.Thr290=, XP_011546052.1:p.Val290Met, XP_011546053.1:p.Val266Met, XR_952745.1:n.2027G>A
C > T
SNP
V338M
VIP No Clinical Annotations available No Variant Annotations available
rs61736512 NC_000022.10:g.42525134C>T, NC_000022.11:g.42129132C>T, NG_008376.3:g.5860G>A, NM_000106.5:c.406G>A, NM_001025161.2:c.353-188G>A, NP_000097.3:p.Val136Met, NT_187682.1:g.51473C>T, NW_004504305.1:g.51459C>T, NW_009646208.1:g.14698C>T, XM_005278353.1:c.363-189G>A, XM_005278354.1:c.107G>A, XM_005278354.3:c.107G>A, XM_011529966.1:c.406G>A, XM_011529967.1:c.406G>A, XM_011529968.1:c.406G>A, XM_011529969.1:c.263G>A, XM_011529970.1:c.353-188G>A, XM_011529971.1:c.263G>A, XM_011529972.1:c.406G>A, XM_011547541.1:c.107G>A, XM_011547750.1:c.263G>A, XM_011547751.1:c.190G>A, XM_011547756.1:c.-903C>T, XM_011548819.1:c.107G>A, XP_005278411.1:p.Arg36His, XP_011528268.1:p.Val136Met, XP_011528269.1:p.Val136Met, XP_011528270.1:p.Val136Met, XP_011528271.1:p.Arg88His, XP_011528273.1:p.Arg88His, XP_011528274.1:p.Val136Met, XP_011545843.1:p.Arg36His, XP_011546052.1:p.Arg88His, XP_011546053.1:p.Val64Ile, XP_011547121.1:p.Arg36His, XR_430455.2:n.-739C>T, XR_952745.1:n.1563G>A
C > T
SNP
V136M
No VIP available CA VA
rs80338792 NC_000017.10:g.62021206C>A, NC_000017.10:g.62021206C>G, NC_000017.10:g.62021206C>T, NC_000017.11:g.63943846C>A, NC_000017.11:g.63943846C>G, NC_000017.11:g.63943846C>T, NG_011699.1:g.34073G>A, NG_011699.1:g.34073G>C, NG_011699.1:g.34073G>T, NM_000334.4:c.3917G>A, NM_000334.4:c.3917G>C, NM_000334.4:c.3917G>T, NP_000325.4:p.Gly1306Ala, NP_000325.4:p.Gly1306Glu, NP_000325.4:p.Gly1306Val, XM_005257566.1:c.3917G>A, XM_005257566.1:c.3917G>C, XM_005257566.1:c.3917G>T, XM_005257566.3:c.3917G>A, XM_005257566.3:c.3917G>C, XM_005257566.3:c.3917G>T, XP_005257623.1:p.Gly1306Ala, XP_005257623.1:p.Gly1306Glu, XP_005257623.1:p.Gly1306Val
C > G
SNP
G1306A
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • Flecainida [INN-Spanish]
  • Flecainide acetate
  • Flecainidum [INN-Latin]
Trade Names
  • Flecaine
  • Tambocor
Brand Mixture Names

PharmGKB Accession Id

PA449646

Type(s):

Drug

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.

Source: Drug Bank

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.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

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.

Source: Drug Bank

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.

Source: Drug Bank

Food Interaction

Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

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).

Source: Drug Bank

Protein Binding

40%

Source: Drug Bank

Absorption

Nearly complete following oral administration.

Source: Drug Bank

Half-Life

20 hours (range 12-27 hours)

Source: Drug Bank

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.

Source: Drug Bank

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 ¿g/mL).

Source: Drug Bank

Chemical Properties

Chemical Formula

C17H20F6N2O3

Source: Drug Bank

Isomeric SMILES

c1cc(c(cc1OCC(F)(F)F)C(=O)NCC2CCCCN2)OCC(F)(F)F

Source: OpenEye

Canonical SMILES

FC(F)(F)COC1=CC(C(=O)NCC2CCCCN2)=C(OCC(F)(F)F)C=C1

Source: Drug Bank

Average Molecular Weight

414.3427

Source: Drug Bank

Monoisotopic Molecular Weight

414.137811746

Source: Drug Bank

SMILES

FC(F)(F)COC1=CC(C(=O)NCC2CCCCN2)=C(OCC(F)(F)F)C=C1

Source: Drug Bank

InChI String

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)

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Antiarrhythmic Pathway, Pharmacodynamics
    Pharmacodynamic pathway of antiarrhythmic drugs in a stylized cardiac myocyte.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
SCN4A (source: Drug Bank)
SCN5A (source: Drug Bank)

Drug Interactions

Interaction Description
amiodarone - flecainide Increases the effect and toxicity of flecainide (source: Drug Bank)
amiodarone - flecainide Increases the effect and toxicity of flecainide (source: Drug Bank)
cimetidine - flecainide Increases serum levels of flecainide (source: Drug Bank)
cimetidine - flecainide Increases serum levels of flecainide (source: Drug Bank)
cisapride - flecainide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
cisapride - flecainide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
duloxetine - flecainide Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank)
duloxetine - flecainide Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank)
flecainide - amiodarone Amiodarone increases the effect and toxicity of flecainide (source: Drug Bank)
flecainide - amiodarone Amiodarone increases the effect and toxicity of flecainide (source: Drug Bank)
flecainide - cimetidine Cimetidine increases serum levels of flecainide (source: Drug Bank)
flecainide - cimetidine Cimetidine increases serum levels of flecainide (source: Drug Bank)
flecainide - cisapride Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
flecainide - cisapride Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
flecainide - duloxetine Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank)
flecainide - duloxetine Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank)
flecainide - mesoridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
flecainide - mesoridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
flecainide - quinupristin This combination presents an increased risk of toxicity (source: Drug Bank)
flecainide - quinupristin This combination presents an increased risk of toxicity (source: Drug Bank)
flecainide - ritonavir Ritonavir increases the toxicity of the anti-arrhythmic (source: Drug Bank)
flecainide - ritonavir Ritonavir increases the toxicity of the anti-arrhythmic (source: Drug Bank)
flecainide - terfenadine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
flecainide - terfenadine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
flecainide - thioridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
flecainide - thioridazine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
mesoridazine - flecainide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
mesoridazine - flecainide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
quinupristin - flecainide This combination presents an increased risk of toxicity (source: Drug Bank)
terfenadine - flecainide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
terfenadine - flecainide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
thioridazine - flecainide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
thioridazine - flecainide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
thiothixene - flecainide May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
thiothixene - flecainide May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
tipranavir - flecainide Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Flecainide. Concomitant therapy is contraindicated. (source: Drug Bank)
toremifene - flecainide 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. (source: Drug Bank)
trazodone - flecainide The 2D6 inhibitor, Trazodone, may increase the efficacy of Flecainide by decreasing Flecainide metabolism and clearance. Monitor for changes in Flecainide efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
trazodone - flecainide The 2D6 inhibitor, Trazodone, may increase the efficacy of Flecainide by decreasing Flecainide metabolism and clearance. Monitor for changes in Flecainide efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
trimipramine - flecainide Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank)
voriconazole - flecainide Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank)
vorinostat - flecainide Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank)
ziprasidone - flecainide Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. (source: Drug Bank)
zuclopenthixol - flecainide 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). (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to flecainide: 12

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
beta1-Adrenergic receptor Arg389Gly polymorphism affects the antiarrhythmic efficacy of flecainide in patients with coadministration of beta-blockers. Pharmacogenetics and genomics. 2016. Doki Kosuke, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Serum flecainide S/R ratio reflects the CYP2D6 genotype and changes in CYP2D6 activity. Drug metabolism and pharmacokinetics. 2015. Doki Kosuke, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The genetics of pro-arrhythmic adverse drug reactions. British journal of clinical pharmacology. 2014. Petropoulou Evmorfia, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Dramatic improvement of myotonia permanens with flecainide: a two-case report of a possible bench-to-bedside pharmacogenetics strategy. European journal of clinical pharmacology. 2013. Desaphy Jean-François, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
CYP2D6 genotype affects age-related decline in flecainide clearance: a population pharmacokinetic analysis. Pharmacogenetics and genomics. 2012. Doki Kosuke, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effects of CYP2D6*10, CYP3A5*3, CYP1A2*1F, and ABCB1 C3435T polymorphisms on the pharmacokinetics of flecainide in healthy Chinese subjects. Drug metabolism and drug interactions. 2012. Hu Miao, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Novel KCNA5 mutation implicates tyrosine kinase signaling in human atrial fibrillation. Heart rhythm : the official journal of the Heart Rhythm Society. 2010. Yang Tao, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Cytochrome P450 2D6. Pharmacogenetics and genomics. 2009. Owen Ryan P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nature medicine. 2009. Watanabe Hiroshi, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effect of CYP2D6 genotype on flecainide pharmacokinetics in Japanese patients with supraventricular tachyarrhythmia. European journal of clinical pharmacology. 2006. Doki Kosuke, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance, and interaction with amiodarone. Clinical pharmacology and therapeutics. 1994. Funck-Brentano C, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0089-0305-10
DrugBank:
DB01195
KEGG Compound:
C07001
PubChem Compound:
3356
PubChem Substance:
181803
46508078
IUPHAR Ligand:
2560
Drugs Product Database (DPD):
1966197
BindingDB:
50131434
ChemSpider:
3239
Therapeutic Targets Database:
DAP000518
FDA Drug Label at DailyMed:
b764c8b8-7e23-4016-830f-68312d84f3d3

Clinical Trials

These are trials that mention flecainide and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

Common Searches

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Sources for PharmGKB drug information: DrugBank, PubChem.