Chemical: Drug
carvedilol

last updated 01/07/2014

1. DPWG Guideline for carvedilol and CYP2D6

Summary

There are currently no dosing recommendations for carvedilol based on CYP2D6 genotype.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for carvedilol based on CYP2D6 genotypes [Article:21412232]. They conclude that there are no recommendations at this time.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
PM (two inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) alleles)No recommendations.Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test.
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)No recommendations.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).
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)No recommendations.----


Annotated Labels

  1. FDA Label for carvedilol and CYP2D6
  2. HCSC Label for carvedilol and CYP2D6

last updated 10/25/2013

1. FDA Label for carvedilol and CYP2D6

Actionable PGx

Summary

Carvedilol is metabolized by CYP2D6 and CYP2C9. The drug label states that carvedilol is affected by the poor metabolizers of debrisoquin (a marker for cytochrome P450 2D6) resulting in higher plasma concentrations of R( + )-carvedilol. Additionally, retrospective analysis of side effects in clinical trials showed that poor CYP2D6 metabolizers had a higher rate of dizziness during up-titration, presumably resulting from vasodilating effects of the higher concentrations of the a-blocking R(+) enantiomer.

Annotation

Carvedilol is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, to reduce cardiovascular mortality in clinically stable patients with left ventricular dysfunction following myocardial infarction, and for the management of essential hypertension. It is a nonselective beta-adrenergic blocking agent with a1-blocking activity.
Carvedilol is a racemic mixture and undergoes stereoselective first-pass metabolism. Cytochrome P450 enzymes responsible for the metabolism of both R(+) and S(-)-carvedilol in human liver microsomes were CYP2D6 and CYP2C9 and to a lesser extent CYP3A4, CYP2C19, CYP1A2, and CYP2E1.

Excerpts from the Carvedilol drug label:

Retrospective analysis of side effects in clinical trials showed that poor 2D6 metabolizers had a higher rate of dizziness during up-titration, presumably resulting from vasodilating effects of the higher concentrations of the a-blocking R(+) enantiomer.

Carvedilol is subject to the effects of genetic polymorphism with poor metabolizers of debrisoquin (a marker for cytochrome P450 2D6) exhibiting 2- to 3-fold higher plasma concentrations of R( + )-carvedilol compared to extensive metabolizers. In contrast, plasma levels of S( - )-carvedilol are increased only about 20% to 25% in poor metabolizers, indicating this enantiomer is metabolized to a lesser extent by cytochrome P450 2D6 than R(+)-carvedilol. The pharmacokinetics of carvedilol do not appear to be different in poor metabolizers of S-mephenytoin (patients deficient in cytochrome P450 2C19).

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Carvedilol drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Diabetes Mellitus
    • Warnings section, Adverse reactions section
    • source: PHONT
  • Heart Failure
    • Indications & usage section, Contraindications section, Warnings section, Adverse reactions section
    • source: PHONT
  • CYP2C9
    • metabolism/PK, Drug interactions section, Pharmacokinetics section
    • source: U.S. Food and Drug Administration
  • CYP2D6
    • metabolism/PK, Drug interactions section, Pharmacokinetics section
    • source: U.S. Food and Drug Administration

last updated 06/08/2015

2. HCSC Label for carvedilol and CYP2D6

Actionable PGx

Summary

The product monograph for carvedilol notes that CYP2D6 poor metabolizers exhibit 2- to 3-fold higher plasma concentrations of R( + )-carvedilol compared to extensive metabolizers. Plasma levels of S( - )-carvedilol are increased only about 20 - 25% in poor metabolizers.

Annotation

Carvedilol is indicated for treatment of congestive heart failure. Carvedilol is a racemic mixture and undergoes stereoselective first-pass metabolism. Excerpt from the carvedilol product monograph:

Carvedilol is subject to genetic polymorphism with poor metabolizers of debrisoquin (deficient in cytochrome P450 2D6) exhibiting 2- to 3-fold higher plasma concentrations of the R( + )-carvedilol compared to extensive metabolizers. In contrast, plasma levels of S( - )-carvedilol are increased only about 20% to 25% in poor metabolizers, indicating that the metabolism of this enantiomer is affected to a lesser extent by cytochrome P450 2D6 than R(+)-carvedilol. The pharmacokinetics of carvedilol enantiomers do not appear to be different in poor metabolizers of S-mephenytoin, i.e. deficient in cytochrome P450 CPY 2C19.

For the complete product monograph text with sections containing pharmacogenetic information highlighted, see the carvedilol product monograph.

*Disclaimer: The contents of this page have not been endorsed by HCSC and are the sole responsibility of PharmGKB.


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.

? = Mouse-over for quick help

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 carvedilol

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA ADRB1 H1 N/A N/A N/A
No VIP available No VIP available VA ADRB1 H2 N/A N/A N/A
No VIP available No VIP available VA ADRB1 H3 N/A N/A N/A
No VIP available No VIP available VA CYP2C19 *1A N/A N/A N/A
No VIP available No VIP available VA CYP2C19 *2A N/A N/A N/A
No VIP available No VIP available VA CYP2C19 *17 N/A N/A N/A
No VIP available No VIP available VA CYP2C9 *1 N/A N/A N/A
No VIP available No VIP available VA CYP2C9 *2 N/A N/A N/A
No VIP available No VIP available VA CYP2C9 *3 N/A N/A N/A
VIP CA VA CYP2D6 *1 N/A N/A N/A
VIP CA VA CYP2D6 *2 N/A N/A N/A
VIP No VIP available VA 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 VA 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
VIP No VIP available No VIP available CYP2D6 *17 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *29 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 Clinical Annotations available VA
CYP2D6 extensive metabolizer genotype N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs1042713 NC_000005.10:g.148826877G=, NC_000005.10:g.148826877G>A, NC_000005.9:g.148206440G=, NC_000005.9:g.148206440G>A, NG_016421.1:g.5285A=, NG_016421.1:g.5285A>G, NM_000024.5:c.46A=, NM_000024.5:c.46A>G, NP_000015.1:p.Arg16=, NP_000015.1:p.Arg16Gly, XM_005268382.1:c.46G=, XM_005268382.1:c.46G>A, XM_005268383.1:c.46G=, XM_005268383.1:c.46G>A, XP_005268439.1:p.Gly16=, XP_005268439.1:p.Gly16Arg, XP_005268440.1:p.Gly16=, XP_005268440.1:p.Gly16Arg, rs17287432, rs17334179, rs17334242, rs17721693, rs17839749, rs17846639, rs17859732, rs3182174, rs3729940, rs52812686, rs56964295
G > A
SNP
R16G
No VIP available CA VA
rs1042714 NC_000005.10:g.148826910G=, NC_000005.10:g.148826910G>C, NC_000005.9:g.148206473G=, NC_000005.9:g.148206473G>C, NG_016421.1:g.5318C=, NG_016421.1:g.5318C>G, NM_000024.5:c.79C=, NM_000024.5:c.79C>G, NP_000015.1:p.Gln27=, NP_000015.1:p.Gln27Glu, XM_005268382.1:c.79G=, XM_005268382.1:c.79G>C, XM_005268383.1:c.79G=, XM_005268383.1:c.79G>C, XP_005268439.1:p.Glu27=, XP_005268439.1:p.Glu27Gln, XP_005268440.1:p.Glu27=, XP_005268440.1:p.Glu27Gln, rs17287411, rs17287474, rs17334200, rs17640526, rs17845338, rs17858183, rs17859733, rs3182175, rs3729941, rs52793394, rs60374884
G > C
G > T
SNP
Q27E
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
No VIP available No Clinical Annotations available VA
rs12233719 NC_000004.11:g.69962449G>T, NC_000004.12:g.69096731G>T, NM_001074.2:c.211G>T, NP_001065.2:p.Ala71Ser, XM_005265702.1:c.-26-1809G>T, XM_005265702.2:c.-26-1809G>T, XM_011532229.1:c.211G>T, XM_011532230.1:c.211G>T, XM_011532231.1:c.-26-1809G>T, XP_011530531.1:p.Ala71Ser, XP_011530532.1:p.Ala71Ser, rs52806684, rs58730779
G > T
SNP
A71S
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
rs1801252 NC_000010.10:g.115804036A>G, NC_000010.11:g.114044277A>G, NG_012187.1:g.5231A>G, NM_000684.2:c.145A>G, NP_000675.1:p.Ser49Gly, rs12720482, rs3740152
A > G
SNP
S49G
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
No VIP available No Clinical Annotations available VA
rs28365063 NC_000004.11:g.69962610A>G, NC_000004.12:g.69096892A>G, NM_001074.2:c.372A>G, NP_001065.2:p.Arg124=, XM_005265702.1:c.-26-1648A>G, XM_005265702.2:c.-26-1648A>G, XM_011532229.1:c.372A>G, XM_011532230.1:c.372A>G, XM_011532231.1:c.-26-1648A>G, XP_011530531.1:p.Arg124=, XP_011530532.1:p.Arg124=, rs45568039, rs60754346
A > G
SNP
R124R
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
No VIP available CA VA
rs4148323 NC_000002.11:g.234669144G>A, NC_000002.12:g.233760498G>A, NG_002601.2:g.175755G>A, NG_033238.1:g.5226G>A, NM_000463.2:c.211G>A, NM_001072.3:c.862-6536G>A, NM_007120.2:c.868-6536G>A, NM_019075.2:c.856-6536G>A, NM_019076.4:c.856-6536G>A, NM_019077.2:c.856-6536G>A, NM_019078.1:c.868-6536G>A, NM_019093.2:c.868-6536G>A, NM_021027.2:c.856-6536G>A, NM_205862.1:c.61-6536G>A, NP_000454.1:p.Gly71Arg, XR_241238.1:n.924-6536G>A, XR_241239.1:n.233G>A, XR_241240.1:n.1023-6536G>A, XR_241241.1:n.942-6536G>A, rs113525835, rs34360183, rs58105808, rs58585123
G > A
SNP
G71R
No VIP available No Clinical Annotations available VA
rs4253778 NC_000022.10:g.46630634G>C, NC_000022.11:g.46234737G>C, NG_012204.1:g.89136G>C, NM_001001928.2:c.1160-396G>C, NM_005036.4:c.1160-396G>C, XM_005261653.1:c.1160-396G>C, XM_005261654.1:c.1160-396G>C, XM_005261655.1:c.1160-396G>C, XM_005261655.2:c.1160-396G>C, XM_005261656.1:c.1160-396G>C, XM_005261656.2:c.1160-396G>C, XM_005261657.1:c.1160-396G>C, XM_005261658.1:c.1160-396G>C, XM_006724269.2:c.1160-396G>C, XM_006724270.2:c.1160-396G>C, XM_011530239.1:c.1160-396G>C, XM_011530240.1:c.1160-396G>C, XM_011530241.1:c.1160-396G>C, XM_011530242.1:c.1160-396G>C, XM_011530243.1:c.1160-396G>C, XM_011530244.1:c.758-396G>C, XM_011530245.1:c.758-396G>C, XR_244379.1:n.1184-396G>C, XR_937869.1:n.1276-396G>C, XR_937870.1:n.1271-396G>C, rs17248629, rs57323063, rs61046783
G > C
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
rs8175347
(TA)6 > (TA)5
(TA)6 > (TA)7
(TA)6 > (TA)8
microsatellite
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • Carvedilolum [Latin]
  • carvedilol
Trade Names
  • Coreg
  • Coreg CR
Brand Mixture Names

PharmGKB Accession Id

PA448817

Type(s):

Drug

Description

Carvedilol is a non-selective beta blocker indicated in the treatment of mild to moderate congestive heart failure (CHF). It blocks beta-1 and beta-2 adrenergic receptors as well as the alpha-1 adrenergic receptors.

Source: Drug Bank

Indication

For the treatment of mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Carvedilol is a racemic mixture in which nonselective beta-adrenoreceptor blocking activity is present in the S(-) enantiomer and alpha-adrenergic blocking activity is present in both R() and S(-) enantiomers at equal potency. Carvedilol's beta-adrenergic receptor blocking ability decreases the heart rate, myocardial contractility, and myocardial oxygen demand. Carvedilol also decreases systemic vascular resistance via its alpha adrenergic receptor blocking properties. Carvedilol and its metabolite BM-910228 (a less potent beta blocker, but more potent antioxidant) have been shown to restore the inotropic responsiveness to Ca ^2^ in OH - free radical-treated myocardium. Carvedilol and its metabolites also prevent OH - radical-induced decrease in sarcoplasmic reticulum Ca 2+-ATPase activity. Therefore, carvedilol and its metabolites may be beneficial in chronic heart failure by preventing free radical damage.

Source: Drug Bank

Pharmacology

Carvedilol is a nonselective beta-adrenergic blocking agent with alpha1-blocking activity and is indicated for the treatment of hypertension and mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin. Carvedilol is a racemic mixture in which nonselective b-adrenoreceptor blocking activity is present in the S(-) enantiomer and a-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol has no intrinsic sympathomimetic activity. The effect of carvedilol's b-adrenoreceptor blocking activity has been demonstrated in animal and human studies showing that carvedilol (1) reduces cardiac output in normal subjects; (2) reduces exercise-and/or isoproterenol-induced tachycardia and (3) reduces reflex orthostatic tachycardia.

Source: Drug Bank

Food Interaction

Take with food, food slows the absorption rate and reduces the incidence of adverse effects (extent of absorption is not affected).

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Carvedilol is metabolized primarily by aromatic ring oxidation and glucuronidation. The oxidative metabolites are further metabolized by conjugation via glucuronidation and sulfation. Demethylation and hydroxylation at the phenol ring produce three active metabolites with b-receptor blocking activity. The 4'-hydroxyphenyl metabolite is approximately 13 times more potent than carvedilol for b-blockade.

Source: Drug Bank

Protein Binding

98%

Source: Drug Bank

Absorption

Carvedilol is rapidly and extensively absorbed following oral administration, with an absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism.

Source: Drug Bank

Half-Life

7-10 hours

Source: Drug Bank

Toxicity

Not expected to be toxic following ingestion.

Source: Drug Bank

Clearance

  • 500-700 mL/min

Source: Drug Bank

Route of Elimination

Carvedilol is extensively metabolized. Less than 2% of the dose was excreted unchanged in the urine.
Carvedilol is metabolized primarily by aromatic ring oxidation and glucuronidation. The oxidative metabolites are further metabolized by conjugation via glucuronidation and sulfation. The metabolites of carvedilol are excreted primarily via the bile into the feces.

Source: Drug Bank

Volume of Distribution

  • 115 L

Source: Drug Bank

Chemical Properties

Chemical Formula

C24H26N2O4

Source: Drug Bank

Isomeric SMILES

COC1=CC=CC=C1OCCNC[C@H](COC2=CC=CC3=C2C4=CC=CC=C4N3)O

Source: Drug Bank

COC1=C(OCCNCC(O)COC2=CC=CC3=C2C2=C(N3)C=CC=C2)C=CC=C1

Source: Drug Bank

Canonical SMILES

COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2

Source: Drug Bank

Average Molecular Weight

406.4742

Source: Drug Bank

Monoisotopic Molecular Weight

406.18925733

Source: Drug Bank

SMILES

COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2

Source: Drug Bank

InChI String

InChI=1S/C24H26N2O4/c1-28-21-10-4-5-11-22(21)29-14-13-25-15-17(27)16-30-23-12-6-9-20-24(23)18-7-2-3-8-19(18)26-20/h2-12,17,25-27H,13-16H2,1H3

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Beta-agonist/Beta-blocker Pathway, Pharmacodynamics
    Simplified pharmacodynamic pathway of drug action on beta 2 adrenergic receptor in a stylized airway cell.

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
ABCB1 (source: Drug Bank)
ADRA1A (source: Drug Bank)
ADRB1 (source: Drug Bank)
ADRB2 (source: Drug Bank)
GJA1 (source: Drug Bank)
KCNH2 (source: Drug Bank)
NDUFC2 (source: Drug Bank)
NPPB (source: Drug Bank)
VCAM1 (source: Drug Bank)
VEGFA (source: Drug Bank)

Drug Interactions

Interaction Description
acetohexamide - carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - acetohexamide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - acetohexamide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - chlorpropamide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - chlorpropamide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - citalopram The SSRI increases the effect of the beta-blocker (source: Drug Bank)
carvedilol - citalopram The SSRI, citalopram, may increase the bradycardic effect of the beta-blocker, carvedilol. (source: Drug Bank)
carvedilol - clonidine Increased hypertension when clonidine stopped (source: Drug Bank)
carvedilol - clonidine Increased hypertension when clonidine stopped (source: Drug Bank)
carvedilol - cyclosporine Increases the effect and toxicity of cyclosporine (source: Drug Bank)
carvedilol - cyclosporine Increases the effect and toxicity of cyclosporine (source: Drug Bank)
carvedilol - digoxin Increases levels/effect of digoxin (source: Drug Bank)
carvedilol - digoxin Increases levels/effect of digoxin (source: Drug Bank)
carvedilol - dihydroergotamine Ischemia with risk of gangrene (source: Drug Bank)
carvedilol - dihydroergotamine Ischemia with risk of gangrene (source: Drug Bank)
carvedilol - dihydroergotoxine Ischemia with risk of gangrene (source: Drug Bank)
carvedilol - dihydroergotoxine Ischemia with risk of gangrene (source: Drug Bank)
carvedilol - disopyramide The beta-blocker increases toxicity of disopyramide (source: Drug Bank)
carvedilol - disopyramide The beta-blocker, carvedilol, may increase toxicity of disopyramide. (source: Drug Bank)
carvedilol - epinephrine Hypertension, then bradycardia (source: Drug Bank)
carvedilol - epinephrine Hypertension, then bradycardia (source: Drug Bank)
carvedilol - ergonovine Ischemia with risk of gangrene (source: Drug Bank)
carvedilol - ergonovine Ischemia with risk of gangrene (source: Drug Bank)
carvedilol - ergotamine Ischemia with risk of gangrene (source: Drug Bank)
carvedilol - ergotamine Ischemia with risk of gangrene (source: Drug Bank)
carvedilol - escitalopram The SSRI increases the effect of the beta-blocker (source: Drug Bank)
carvedilol - escitalopram The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, carvedilol. (source: Drug Bank)
carvedilol - fenoterol Antagonism (source: Drug Bank)
carvedilol - fenoterol Antagonism (source: Drug Bank)
carvedilol - fluoxetine The SSRI increases the effect of the beta-blocker (source: Drug Bank)
carvedilol - fluoxetine The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, carvedilol. (source: Drug Bank)
carvedilol - formoterol Antagonism (source: Drug Bank)
carvedilol - formoterol Antagonism (source: Drug Bank)
carvedilol - glibenclamide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - glibenclamide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - gliclazide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - glipizide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - glisoxepide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - glisoxepide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - glycodiazine The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - glycodiazine The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - ibuprofen Risk of inhibition of renal prostaglandins (source: Drug Bank)
carvedilol - ibuprofen Risk of inhibition of renal prostaglandins (source: Drug Bank)
carvedilol - indomethacin Risk of inhibition of renal prostaglandins (source: Drug Bank)
carvedilol - indomethacin Risk of inhibition of renal prostaglandins (source: Drug Bank)
carvedilol - insulin-glargine The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - isoproterenol Antagonism (source: Drug Bank)
carvedilol - isoproterenol Antagonism (source: Drug Bank)
carvedilol - lidocaine The beta-blocker increases the effect and toxicity of lidocaine (source: Drug Bank)
carvedilol - lidocaine The beta-blocker, carvedilol, may increase the effect and toxicity of lidocaine. (source: Drug Bank)
carvedilol - methysergide Ischemia with risk of gangrene (source: Drug Bank)
carvedilol - methysergide Ischemia with risk of gangrene (source: Drug Bank)
carvedilol - orciprenaline Antagonism (source: Drug Bank)
carvedilol - orciprenaline Antagonism (source: Drug Bank)
carvedilol - paroxetine The SSRI increases the effect of the beta-blocker (source: Drug Bank)
carvedilol - paroxetine The SSRI, paroxetine, may increase the bradycardic effect of the beta-blocker, carvedilol. (source: Drug Bank)
carvedilol - pirbuterol Antagonism (source: Drug Bank)
carvedilol - pirbuterol Antagonism (source: Drug Bank)
carvedilol - piroxicam Risk of inhibition of renal prostaglandins (source: Drug Bank)
carvedilol - piroxicam Risk of inhibition of renal prostaglandins (source: Drug Bank)
carvedilol - prazosin Risk of hypotension at the beginning of therapy (source: Drug Bank)
carvedilol - prazosin Risk of hypotension at the beginning of therapy (source: Drug Bank)
carvedilol - procaterol Antagonism (source: Drug Bank)
carvedilol - procaterol Antagonism (source: Drug Bank)
carvedilol - repaglinide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - repaglinide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - salbutamol Antagonism (source: Drug Bank)
carvedilol - salbutamol Antagonism (source: Drug Bank)
carvedilol - salmeterol Antagonism (source: Drug Bank)
carvedilol - salmeterol Antagonism (source: Drug Bank)
carvedilol - sertraline The SSRI increases the effect of the beta-blocker (source: Drug Bank)
carvedilol - sertraline The SSRI, sertraline, may increase the bradycardic effect of the beta-blocker, carvedilol. (source: Drug Bank)
carvedilol - terbutaline Antagonism (source: Drug Bank)
carvedilol - terbutaline Antagonism (source: Drug Bank)
carvedilol - tolazamide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - tolazamide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - tolbutamide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - tolbutamide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - verapamil Increased effect of both drugs (source: Drug Bank)
carvedilol - verapamil Increased effect of both drugs (source: Drug Bank)
chlorpropamide - carvedilol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
chlorpropamide - carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
citalopram - carvedilol The SSRI increases the effect of the beta-blocker (source: Drug Bank)
citalopram - carvedilol The SSRI, citalopram, may increase the bradycardic effect of the beta-blocker, carvedilol. (source: Drug Bank)
clonidine - carvedilol Increased hypertension when clonidine stopped (source: Drug Bank)
clonidine - carvedilol Increased hypertension when clonidine stopped (source: Drug Bank)
cyclosporine - carvedilol Carvedilol increases the effect and toxicity of cyclosporine (source: Drug Bank)
cyclosporine - carvedilol Carvedilol increases the effect and toxicity of cyclosporine (source: Drug Bank)
digoxin - carvedilol Carvedilol increases levels/effect of digoxin (source: Drug Bank)
digoxin - carvedilol Carvedilol increases levels/effect of digoxin (source: Drug Bank)
dihydroergotamine - carvedilol Ischemia with risk of gangrene (source: Drug Bank)
dihydroergotamine - carvedilol Ischemia with risk of gangrene (source: Drug Bank)
disopyramide - carvedilol The beta-blocker increases toxicity of disopyramide (source: Drug Bank)
disopyramide - carvedilol The beta-blocker, carvedilol, may increase the toxicity of disopyramide. (source: Drug Bank)
epinephrine - carvedilol Hypertension, then bradycardia (source: Drug Bank)
epinephrine - carvedilol Hypertension, then bradycardia (source: Drug Bank)
ergotamine - carvedilol Ischemia with risk of gangrene (source: Drug Bank)
ergotamine - carvedilol Ischemia with risk of gangrene (source: Drug Bank)
escitalopram - carvedilol The SSRI increases the effect of the beta-blocker (source: Drug Bank)
escitalopram - carvedilol The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, carvedilol. (source: Drug Bank)
fenoterol - carvedilol Antagonism (source: Drug Bank)
fenoterol - carvedilol Antagonism (source: Drug Bank)
fluoxetine - carvedilol The SSRI increases the effect of the beta-blocker (source: Drug Bank)
fluoxetine - carvedilol The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, carvedilol. (source: Drug Bank)
formoterol - carvedilol Antagonism (source: Drug Bank)
formoterol - carvedilol Antagonism (source: Drug Bank)
glibenclamide - carvedilol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
glibenclamide - carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
gliclazide - carvedilol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide - carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
ibuprofen - carvedilol Risk of inhibition of renal prostaglandins (source: Drug Bank)
ibuprofen - carvedilol Risk of inhibition of renal prostaglandins (source: Drug Bank)
indomethacin - carvedilol Risk of inhibition of renal prostaglandins (source: Drug Bank)
indomethacin - carvedilol Risk of inhibition of renal prostaglandins (source: Drug Bank)
insulin-glargine - carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
insulin-glargine - carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
methysergide - carvedilol Ischemia with risk of gangrene (source: Drug Bank)
methysergide - carvedilol Ischemia with risk of gangrene (source: Drug Bank)
orciprenaline - carvedilol Antagonism (source: Drug Bank)
orciprenaline - carvedilol Antagonism (source: Drug Bank)
pipobroman - carvedilol Antagonism (source: Drug Bank)
piroxicam - carvedilol Risk of inhibition of renal prostaglandins (source: Drug Bank)
piroxicam - carvedilol Risk of inhibition of renal prostaglandins (source: Drug Bank)
prazosin - carvedilol Risk of hypotension at the beginning of therapy (source: Drug Bank)
prazosin - carvedilol Risk of hypotension at the beginning of therapy (source: Drug Bank)
repaglinide - carvedilol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
repaglinide - carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
terazosin - carvedilol Increased risk of hypotension. Initiate concomitant therapy cautiously. (source: Drug Bank)
terbutaline - carvedilol Antagonism (source: Drug Bank)
terbutaline - carvedilol Antagonism (source: Drug Bank)
topotecan - carvedilol The p-glycoprotein inhibitor, Carvedilol, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided. (source: Drug Bank)
trazodone - carvedilol The 2D6 inhibitor, Trazodone, may increase the efficacy of Carvedilol by decreasing Carvedilol metabolism and clearance. Monitor for changes in Carvedilol efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
trazodone - carvedilol The 2D6 inhibitor, Trazodone, may increase the efficacy of Carvedilol by decreasing Carvedilol metabolism and clearance. Monitor for changes in Carvedilol efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
treprostinil - carvedilol Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use. (source: Drug Bank)

Curated Information ?

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

May Treat
Contraindicated With

Publications related to carvedilol: 43

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Variation in the CYP2D6 genotype is not associated with carvedilol dose changes in patients with heart failure. Journal of clinical pharmacy and therapeutics. 2014. Shihmanter R, et al. PubMed
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Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
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Impact of the beta1-Adrenoceptor Arg389Gly Polymorphism on Heart-Rate Responses to Bisoprolol and Carvedilol in Heart-Failure Patients. Clinical pharmacology and therapeutics. 2012. Rau T, et al. PubMed
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Pharmacogenomics of the heptahelical receptor regulators G-protein-coupled receptor kinases and arrestins: the known and the unknown. Pharmacogenomics. 2012. Lymperopoulos Anastasios, et al. PubMed
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A Common beta1-Adrenergic Receptor Polymorphism Predicts Favorable Response to Rate-Control Therapy in Atrial Fibrillation. Journal of the American College of Cardiology. 2012. Parvez Babar, et al. PubMed
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Carvedilol Reduces Aortic Wave Reflection and Improves Left Ventricular/Vascular Coupling: A Comparison With Atenolol (CENTRAL Study). Journal of clinical hypertension (Greenwich, Conn.). 2011. Shah Niren K, et al. PubMed
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Combinatorial pharmacogenetic interactions of bucindolol and beta1, alpha2C adrenergic receptor polymorphisms. PloS one. 2012. O'Connor Christopher M, et al. PubMed
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The Arg389Gly beta1-adrenoceptor gene polymorphism influences the acute effects of beta-adrenoceptor blockade on contractility in the human heart. Clinical research in cardiology : official journal of the German Cardiac Society. 2011. Huntgeburth Michael, et al. PubMed
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Carvedilol pharmacokinetics and pharmacodynamics in relation to CYP2D6 and ADRB pharmacogenetics. Pharmacogenomics. 2011. Sehrt Daniel, et al. PubMed
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Pharmacogenomics: the genetics of variable drug responses. Circulation. 2011. Roden Dan M, et al. PubMed
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Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
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Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al. PubMed
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Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
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beta-blocker therapy and heart rate control during exercise testing in the general population: role of a common G-protein beta-3 subunit variant. Pharmacogenomics. 2010. Dörr Marcus, et al. PubMed
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Combination antihypertensive treatment: is initiation order important?. Journal of clinical hypertension (Greenwich, Conn.). 2010. Gums John G, et al. PubMed
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Relation of ADRB1, CYP2D6, and UGT1A1 polymorphisms with dose of, and response to, carvedilol or metoprolol therapy in patients with chronic heart failure. The American journal of cardiology. 2010. Baudhuin Linnea M, et al. PubMed
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Haplotypes of the adrenergic system predict the blood pressure response to beta-blockers in women with essential hypertension. Pharmacogenomics. 2010. Filigheddu Fabiana, et al. PubMed
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Role of beta-adrenergic receptor gene polymorphisms in the long-term effects of beta-blockade with carvedilol in patients with chronic heart failure. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy. 2010. Metra Marco, et al. PubMed
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Very important pharmacogene summary ADRB2. Pharmacogenetics and genomics. 2010. Litonjua Augusto A, et al. PubMed
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Cytochrome P450 2D6. Pharmacogenetics and genomics. 2009. Owen Ryan P, et al. PubMed
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Medicinal Chemistry of Drugs used in Diabetic Cardiomyopathy. Current medicinal chemistry. 2009. Adeghate E, et al. PubMed
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Genetic variation in the CYP2D6 gene is associated with a lower heart rate and blood pressure in beta-blocker users. Clinical pharmacology and therapeutics. 2009. Bijl M J, et al. PubMed
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The beta2 adrenergic receptor Gln27Glu polymorphism affects insulin resistance in patients with heart failure: possible modulation by choice of beta blocker. Journal of cardiovascular pharmacology. 2008. Vardeny Orly, et al. PubMed
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Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed
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Interaction between PPARA genotype and beta-blocker treatment influences clinical outcomes following acute coronary syndromes. Pharmacogenomics. 2008. Cresci Sharon, et al. PubMed
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Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Zhou S-F. PubMed
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A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. Nature medicine. 2008. Liggett Stephen B, et al. PubMed
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Arg389Gly-beta1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol. Pharmacogenetics and genomics. 2007. Chen Lu, et al. PubMed
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Synergistic polymorphisms of beta1 and alpha2C-adrenergic receptors and the influence on left ventricular ejection fraction response to beta-blocker therapy in heart failure. Pharmacogenetics and genomics. 2007. Lobmeyer Maximilian T, et al. PubMed
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Evaluation of effects of polymorphism for metabolic enzymes on pharmacokinetics of carvedilol by population pharmacokinetic analysis. Biological & pharmaceutical bulletin. 2007. Takekuma Yoh, et al. PubMed
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beta1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. Clinical pharmacology and therapeutics. 2006. Liu Jie, et al. PubMed
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A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure. Proceedings of the National Academy of Sciences of the United States of America. 2006. Liggett Stephen B, et al. PubMed
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Multiple regression analysis of pharmacogenetic variability of carvedilol disposition in 54 healthy Japanese volunteers. Biological & pharmaceutical bulletin. 2006. Honda Mutsuko, et al. PubMed
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Contribution of polymorphisms in UDP-glucuronosyltransferase and CYP2D6 to the individual variation in disposition of carvedilol. Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques. 2006. Takekuma Yoh, et al. PubMed
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Beta1-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to beta-blocker therapy. Pharmacogenetics and genomics. 2005. Terra Steven G, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
beta-Adrenergic receptor polymorphisms and responses during titration of metoprolol controlled release/extended release in heart failure. Clinical pharmacology and therapeutics. 2005. Terra Steven G, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Association between beta-1 and beta-2 adrenergic receptor gene polymorphisms and the response to beta-blockade in patients with stable congestive heart failure. Pharmacogenetics and genomics. 2005. de Groote Pascal, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Gly389Arg polymorphism of beta1-adrenergic receptor is associated with the cardiovascular response to metoprolol. Clinical pharmacology and therapeutics. 2003. Liu Jie, et al. PubMed
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Beta 1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure. Nature medicine. 2003. Mialet Perez Jeanne, et al. PubMed
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An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals with heart failure: a MERIT-HF sub-study. European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology. 2003. White Hazel L, et al. PubMed
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Beta 1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clinical pharmacology and therapeutics. 2003. Johnson Julie A, et al. PubMed
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Beta-adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure. Pharmacogenetics. 2003. Kaye David M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A common beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to beta-blockade. Clinical pharmacology and therapeutics. 2003. Sofowora G G, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0228-2175-11
DrugBank:
DB01136
ChEBI:
3441
KEGG Compound:
C06875
KEGG Drug:
D00255
PubChem Compound:
2585
PubChem Substance:
189887
46505146
IUPHAR Ligand:
551
Drugs Product Database (DPD):
2252317
BindingDB:
25759
ChemSpider:
2487
Therapeutic Targets Database:
DAP000135
FDA Drug Label at DailyMed:
a6eb861c-085e-442a-8e71-722587493d5d

Clinical Trials

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Sources for PharmGKB drug information: DrugBank, PubChem.