PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
digoxin

2D structure

Overview

Generic Names: Digitalis Glycoside
Trade Names: Cardoxin; Cogoxin; Cordioxil; Davoxin; Digacin; Digitekt; Digoxin Pediatric; Dilanacin; Dixina; Dokim; Dynamos; Eudigox; Homolle's Digitalin; Lanacordin; Lanacrist; Lanicor; Lanoxicaps; Lanoxin; Lenoxicaps; Lenoxin; Longdigox; Neo-Lanicor; Neodioxanin; Rougoxin; SK-Digoxin; Stillacor; Vanoxin
PharmGKB Accession Id: PA449319

Description

A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666) (source: Drug Bank)

Indication

For the treatment and management of congestive cardiac insufficiency, arrhythmias and heart failure. (source: Drug Bank)

ATC Therapeutic Categories

  • C01AA:Digitalis glycosides
  • V03AB:Antidotes

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Digoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential. (source: Drug Bank)

Pharmacology

Digoxin, a cardiac glycoside similar to digitoxin, is used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation. (source: Drug Bank)

Food Interactions

Avoid avocado.
Avoid bran and high fiber foods within 2 hours of taking this medication.
Avoid excess salt/sodium unless otherwise instructed by your physician.
Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.
Avoid salt substitutes containing potassium.
Limit garlic, ginger, gingko, and horse chestnut. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic (but not dependent upon the cytochrome P-450 system). The end metabolites, which include 3 b-digoxigenin, 3-keto-digoxigenin, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation. (source: Drug Bank)

Protein Binding

25% (source: Drug Bank)

Absorption

Absorption of digoxin from the elixir pediatric formulation has been demonstrated to be 70% to 85% complete (90% to 100% from the capsules, and 60% to 80% for tablets). (source: Drug Bank)

Toxicity

Toxicity includes ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias, or heart block. LD<sub>50</sub> = 7.8 mg/kg (orally in mice). (source: Drug Bank)

Isomeric SMILES Code:

C[C@@H]1[C@H]([C@H](C[C@@H](O1)O[C@@H]2[C@H](O[C@H](C[C@@H]2O)O[C@@H]3[C@H](O[C@H](C[C@@H]3O)O[C@H]4CC[C@]5([C@@H](C4)CC[C@@H]6[C@@H]5C[C@H]([C@]7([C@@]6(CC[C@@H]7C8=CC(=O)OC8)O)C)O)C)C)C)O)O (source: Drug Bank)

In-Depth Annotations (In-Depth Annotation)

  1. rs1045642 at chr7:86976581 in ABCB1
    Risk or phenotype-associated allele: none. Phenotype: No association with digoxin disposition (AUC, C(max), T(max)) after a single oral dose. Study size: 50. Study population/ethnicity: Healthy, unrelated, white male non-smokers, aged 18-40, from Berlin, Germany. Significance metric(s): p >= 0.3. Type of association: GN; PK.
    Variant Name:
    ABCB1:3435T>C, Ile1145Ile
    Related Drugs:
    digoxin
    Evidence:
    PMID:12492608
    http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforABCB1-3435
  2. rs1045642 at chr7:86976581 in ABCB1
    Risk or phenotype-associated allele: TT genotype. Phenotype: Decreased digoxin absorption after direct delivery to the surface of the duodenum by endoscope. Study size: 11 (5 CC genotype, 6 TT genotype). Study population/ethnicity: Unrelated, healthy subjects from Kobe, Japan. Significance metric(s): p = 0.007. Type of association: GN; PK.
    Variant Name:
    ABCB1:3435T>C, Ile1145Ile
    Related Drugs:
    digoxin
    Evidence:
    PMID:12739761
    http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforABCB1-3435

Curated Annotations (Curated Annotation)

  1. rs1045642 at chr7:86976581 in ABCB1
    Functional study of rs1045642 (3435C>T) and rs1128503 (2677G>T/A): in LLC-PK1 cells expressing wild-type (2677G/3435C) or polymorphic (2677G/3435T, 2677A/3435C, 2677A/3435T, 2677T/3435C, 2677T/3435T) constructs of ABCB1 in vitro, no significant differences were observed in transcellular efflux of structurally diverse P-gp substrates, verapamil, digoxin, vinblastine or cyclosporin A.
    Variant Name:
    ABCB1: c.3435C>T, mRNA 3853C>T
    Related Drugs:
    cyclosporine, digoxin, verapamil, vinblastine
    Evidence:
    PMID:12781336
  2. rs1045642 at chr7:86976581 in ABCB1
    Functional study of rs1045642 (3435C>T) and rs2032582 (2677G>T/A): in LLC-PK1 cells expressing wild-type (2677G/3435C) or polymorphic (2677G/3435T, 2677A/3435C, 2677A/3435T, 2677T/3435C, 2677T/3435T) constructs of ABCB1 in vitro, no significant differences were observed in transcellular efflux of structurally diverse P-gp substrates, verapamil, digoxin, vinblastine or cyclosporin A.
    Variant Name:
    ABCB1: c.3435C>T, mRNA 3853C>T, p.Ile1145Ile
    Related Drugs:
    cyclosporine, digoxin, verapamil, vinblastine
    Evidence:
    PMID:12781336
  3. rs1045642 at chr7:86976581 in ABCB1
    Risk or phenotype-associated allele: None. Phenotype: Efflux of P-glycoprotein substrates (verapamil; digoxin; vinblastine; cyclosporin A) in vitro were not significantly affected by combined mutations for rs1128503 (2677G>T/A) and rs1045642 (3435C>T) in LLC-PK1 cell lines. Study size: Triplicate cell assays. Study population/ethnicity: N/A. Significance metric(s): Not significant, p > 0.05. Type of association: FA
    Variant Name:
    ABCB1:3435C>T, mRNA 3853C>T, Ile1145Ile
    Related Drugs:
    cyclosporine, digoxin, verapamil, vinblastine
    Evidence:
    PMID:12781336
  4. rs1045642 at chr7:86976581 in ABCB1
    Risk or phenotype-associated allele: TT genotype. Phenotype: Decreased expression of intestinal ABCB1 (P-gp) (p = 0.056, n = 21), and increased plasma levels of digoxin relative to the CC genotype (p = 0.006, n = 14). Study size: 21 duodenum samples, and 14 PK subjects. Study population/ethnicity: Caucasians from Germany. Significance metric(s): p = 0.006 - 0.056. Type of association: GN; PK; FA.
    Variant Name:
    ABCB1:3435T>C, Ile1145Ile
    Related Drugs:
    digoxin
    Evidence:
    PMID:10716719
  5. rs2032582 at chr7:86998554 in ABCB1
    Functional study of rs1045642 (3435C>T) and rs2032582 (2677G>T/A): in LLC-PK1 cells expressing wild-type (2677G/3435C) or polymorphic (2677G/3435T, 2677A/3435C, 2677A/3435T, 2677T/3435C, 2677T/3435T) constructs of ABCB1 in vitro, no significant differences were observed in transcellular efflux of structurally diverse P-gp substrates, verapamil, digoxin, vinblastine or cyclosporin A.
    Variant Name:
    ABCB1: c.2677G>T/A, mRNA 3095G>T/A, p.Ala893Ser/Thr
    Related Drugs:
    cyclosporine, digoxin, verapamil, vinblastine
    Evidence:
    PMID:12781336
  6. rs2032582 at chr7:86998554 in ABCB1
    Functional study of rs1045642 (3435C>T) and rs1128503 (2677G>T/A): in LLC-PK1 cells expressing wild-type (2677G/3435C) or polymorphic (2677G/3435T, 2677A/3435C, 2677A/3435T, 2677T/3435C, 2677T/3435T) constructs of ABCB1 in vitro, no significant differences were observed in transcellular efflux of structurally diverse P-gp substrates, verapamil, digoxin, vinblastine or cyclosporin A.
    Variant Name:
    ABCB1: c.2677G>T/A, mRNA 3095G>T/A, p.Ala893Ser/Thr
    Related Drugs:
    cyclosporine, digoxin, verapamil, vinblastine
    Evidence:
    PMID:12781336
  7. rs2032582 at chr7:86998554 in ABCB1
    893Ser-expressing (ABCB1:2677G>T (Ala893Ser)) cells showed 47% lower intracellular digoxin concentration (p < 0.002) than Ala893-expressing cells; and 893Ser/Ser homozygotes showed statistically different fenofexadine area under the concentration curve (AUC) values for 0-4 hours (p = 0.054) than 893Ala/Ala homozygotes.
    Variant Name:
    ABCB1:2677G>T/A, mRNA 3095G>T/A, Ala893Ser/Thr
    Related Drugs:
    digoxin, fexofenadine
    Evidence:
    PMID:11503014
  8. rs1128503 at chr7:87017537 in ABCB1
    Risk or phenotype-associated allele: None. Phenotype: Efflux of P-glycoprotein substrates (verapamil; digoxin; vinblastine; cyclosporin A) in vitro were not significantly affected by combined mutations for rs1128503 (2677G>T/A) and rs1045642 (3435C>T) in LLC-PK1 cell lines. Study size: Triplicate cell assays. Study population/ethnicity: N/A. Significance metric(s): Not significant, p > 0.05. Type of association: FA
    Variant Name:
    ABCB1:2677G>T/A, mRNA 3095G>T/A, Ala893Ser/Thr
    Related Drugs:
    cyclosporine, digoxin, verapamil, vinblastine
    Evidence:
    PMID:12781336
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  • CO
  • PD
  • PK
  • FA
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
ABCC1
  •   
  •   
  •   
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
ABCC2
  •   
  •   
  •   
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
ABCG2
  •   
  •   
  •   
  • FA
  •   
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
ATP1A1
  •   
  • PD
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ATP1A2
  •   
  • PD
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ATP1A3
  •   
  • PD
  •   
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C19
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  • CO
  • PD
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  •   
  •   
  • PK
  •   
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Has annotations
SLCO1B1
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
SLCO1B3
  •   
  •   
  • PK
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SLCO4C1
  •   
  •   
  • PK
  • FA
  •   
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
ATP1A1 Uncurated Annotation (source: Drug Bank)
SLCO1B1 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
azithromycin
  • CO
  • PD
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
clarithromycin
  • CO
  • PD
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
erythromycin
  • CO
  • PD
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Macrolides
  • CO
  • PD
  • PK
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
acarbose Uncurated Annotation Acarbose decreases the effect of digoxin (source: Drug Bank)
alprazolam Uncurated Annotation The benzodiazepine increases the effect of digoxin (source: Drug Bank)
amiodarone Uncurated Annotation Amiodarone increases the effect of digoxin (source: Drug Bank)
bendroflumethiazide Uncurated Annotation Possible electrolyte variations and arrhythmias (source: Drug Bank)
bleomycin Uncurated Annotation The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
bumetanide Uncurated Annotation Possible electrolyte variations and arrhythmias (source: Drug Bank)
carmustine Uncurated Annotation The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
carvedilol Uncurated Annotation Carvedilol increases levels/effect of digoxin (source: Drug Bank)
chlorothiazide Uncurated Annotation Possible electrolyte variations and arrhythmias (source: Drug Bank)
chlorthalidone Uncurated Annotation Possible electrolyte variations and arrhythmias (source: Drug Bank)
cholestyramine Uncurated Annotation The resin decreases the effect of digoxin (source: Drug Bank)
clarithromycin Uncurated Annotation The macrolide increases the effect of digoxin in 10% of patients (source: Drug Bank)
colestipol Uncurated Annotation The resin decreases the effect of digoxin (source: Drug Bank)
cyclophosphamide Uncurated Annotation The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
cyclosporine Uncurated Annotation Cyclosporine increases the effect of digoxin (source: Drug Bank)
cyclothiazide Uncurated Annotation Possible electrolyte variations and arrhythmias (source: Drug Bank)
cytarabine Uncurated Annotation The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
diazepam Uncurated Annotation The benzodiazepine increases the effect of digoxin (source: Drug Bank)
doxorubicin Uncurated Annotation The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
doxycycline Uncurated Annotation The tetracycline increases the effect of digoxin in 10% of patients (source: Drug Bank)
erythromycin Uncurated Annotation The macrolide increases the effect of digoxin in 10% of patients (source: Drug Bank)
ethacrynic acid Uncurated Annotation Possible electrolyte variations and arrhythmias (source: Drug Bank)
furosemide Uncurated Annotation Possible electrolyte variations and arrhythmias (source: Drug Bank)
gatifloxacin Uncurated Annotation Gatifloxacin increases the effect of digoxin (source: Drug Bank)
hydrochlorothiazide Uncurated Annotation Possible electrolyte variations and arrhythmias (source: Drug Bank)
indapamide Uncurated Annotation Possible electrolyte variations and arrhythmias (source: Drug Bank)
itraconazole Uncurated Annotation Itraconazole increases the effect of digoxin (source: Drug Bank)
levothyroxine Uncurated Annotation The thyroid hormones decreases the effect of digoxin (source: Drug Bank)
methimazole Uncurated Annotation The antithyroid agent increases the effect of digoxin (source: Drug Bank)
methotrexate Uncurated Annotation The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
minocycline Uncurated Annotation The tetracycline increases the effect of digoxin in 10% of patients (source: Drug Bank)
oxytetracycline Uncurated Annotation The tetracycline increases the effect of digoxin in 10% of patients (source: Drug Bank)
penicillamine Uncurated Annotation Penicillamine decreases the effect of digoxin (source: Drug Bank)
prazosin Uncurated Annotation Prazosin increases the effect of digoxin (source: Drug Bank)
procarbazine Uncurated Annotation The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
propafenone Uncurated Annotation Propafenone increases the effect of digoxin (source: Drug Bank)
propylthiouracil Uncurated Annotation The antithyroid agent increases the effect of digoxin (source: Drug Bank)
quinidine Uncurated Annotation Quinine/quinidine increases the effect of digoxin (source: Drug Bank)
quinine Uncurated Annotation Quinine/quinidine increases the effect of digoxin (source: Drug Bank)
rabeprazole Uncurated Annotation Rabeprazole increases the effect of digoxin (source: Drug Bank)
ritonavir Uncurated Annotation Ritonavir increases levels/effect of digoxin (source: Drug Bank)
spironolactone Uncurated Annotation Increased digoxin levels and decreased effect in presence of spironolactone (source: Drug Bank)
sulfasalazine Uncurated Annotation Sulfasalazine decreases the effect of digoxin (source: Drug Bank)
telithromycin Uncurated Annotation Telithromycin may increase levels of digoxin (source: Drug Bank)
telmisartan Uncurated Annotation Telmisartan increases the effect of digoxin (source: Drug Bank)
tetracycline Uncurated Annotation The tetracycline increases the effect of digoxin in 10% of patients (source: Drug Bank)
tolbutamide Uncurated Annotation Tolbutamide increases the effect of digoxin (source: Drug Bank)
verapamil Uncurated Annotation Verapamil increases the effect of digoxin (source: Drug Bank)
vincristine Uncurated Annotation The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Arrhythmias, Cardiac
  • CO
  • PD
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Atrial Fibrillation
  •   
  •   
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Drug interaction with drug
  •   
  •   
  • PK
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Heart Failure
  • CO
  • PD
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Kidney Failure
  •   
  •   
  • PK
  •   
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00390
KEGG Compound ID:
C06956
KEGG Drug ID:
D00298
PubChem Compound ID:
30322
PubChem Substance ID:
172469

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

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