PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
amiodarone

2D structure

Overview

Generic Names: Amiodarona [INN-Spanish]; Amiodarone Base; Amiodarone HCL; Amiodarone Hydrochloride; Amiodaronum [INN-Latin]
IUPAC Name: (2-butyl-1-benzofuran-3-yl)-[4-(2-diethylaminoethoxy)-3,5-diiodophenyl]methanone
Trade Names: Aminodarone; Amio-Aqueous IV; Amiodarons; Aratac; Arycor; Cordarone; Cordarone Intravenous; Labaz; Pacerone; pms-Amiodarone
PharmGKB Accession Id: PA448383

Description

An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [PubChem]

Indication

Intravenously, for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy. Orally, for the treatment of life-threatening recurrent ventricular arrhythmias such as recurrent ventricular fibrillation and recurrent hemodynamically unstable ventricular tachycardia.

ATC Therapeutic Category

  • C01BD:Antiarrhythmics, class III

Pharmacology and Interactions

Mechanism Of Action

The antiarrhythmic effect of amiodarone may be due to at least two major actions. It prolongs the myocardial cell-action potential (phase 3) duration and refractory period and acts as a noncompetitive a- and b-adrenergic inhibitor.

Pharmacology

Amiodarone belongs to a class of drugs called Vaughan-Williams Class III antiarrhythmic agents. It is used in the treatment of a wide range of cardiac tachyarhthmias, including both ventricular and supraventricular (atrial) arrhythmias. After intravenous administration in man, amiodarone relaxes vascular smooth muscle, reduces peripheral vascular resistance (afterload), and slightly increases cardiac index. Amiodarone prolongs phase 3 of the cardiac action potential. It has numerous other effects however, including actions that are similar to those of antiarrhythmic classes Ia, II, and IV. Amiodarone shows beta blocker-like and calcium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects.

Food Interactions

Grapefruit and grapefruit juice should be avoided throughout treatment. Grapefruit can significantly increase serum levels of this product. Take without regard to meals.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Amiodarone is extensively metabolized in the liver via CYP2C8 (under 1% unchanged in urine), and can effect the metabolism of numerous other drugs. The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties. The metabolism of amiodarone is inhibited by grapefruit juice, leading to elevated serum levels of amiodarone.

Protein Binding

>96%

Absorption

Slow and variable (about 20 to 55% of an oral dose is absorbed).

Half Life

58 days (range 15-142 days)

Toxicity

Intravenous, mouse: LD50 = 178 mg/kg. Some side effects have a significant mortality rate: specifically, hepatitis, exacerbation of asthma and congestive failure, and pneumonitis.

Chemical Properties

Chemical Formula:

C25H29I2NO3

SMILES Code:

CCCCc1c(c2ccccc2o1)C(=O)c3cc(c(c(c3)I)OCCN(CC)CC)I

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

645.3116 / 645.0237

Curated Annotations (Curated Annotation)

  1. rs12720441 at chr7:150278237 in KCNH2
    Mutation may be responsible for response to amiodarone
    Variant Name:
    R784W
    Related Drugs:
    amiodarone
    Evidence:
    PMID:11997281
  2. rs11572177 at chr10:96787260 in CYP2C8
    Variant was identified in a cohort of 54 Japanese individuals, who were administered the anti-arrhythmic drug amiodarone. (HapMap SNP)
    Related Drugs:
    amiodarone
    Evidence:
    PMID:15618689
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

Curated Information

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
  •   
  •   
  •   
  • FA
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Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC8
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC9
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
ADRA1D
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
ADRA2A
  •   
  • PD
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  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ADRB1
  •   
  • PD
  •   
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  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ADRB2
  •   
  • PD
  •   
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
ANK2
  •   
  • PD
  •   
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  •   
Pathways
Phenotype data available No genotype data Literature annotations available Not annotated
ATP1A1
  •   
  • PD
  •   
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
ATP2A1
  •   
  • PD
  •   
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
ATP2A2
  •   
  • PD
  •   
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
CACNA1C
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
CACNA1D
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
CACNA1G
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
CACNA1H
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data No literature annotations Not annotated
CACNB2
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
CASQ1
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
CASQ2
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
CHRM2
  •   
  • PD
  •   
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP2C8
  •   
  •   
  • PK
  • FA
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  •   
  •   
  • PK
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  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
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  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Has annotations
CYP2J2
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  • PK
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  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
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  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
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  •   
  • PK
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  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
DSP
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
FKBP1B
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
GJA1
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
GJA5
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
GJD3
  •   
  • PD
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
HCN2
  •   
  • PD
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
HCN4
  •   
  • PD
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  •   
Pathways
Phenotype data available No genotype data Literature annotations available Not annotated
JUP
  •   
  • PD
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNA5
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNAB2
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
KCND3
  •   
  • PD
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  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNE1
  •   
  • PD
  •   
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  •   
Pathways
No phenotype data Genotype Data Available No literature annotations Not annotated
KCNE1L
  •   
  • PD
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  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNE2
  •   
  • PD
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  •   
  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
KCNE3
  •   
  • PD
  •   
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
KCNE4
  •   
  • PD
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  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Has annotations
KCNH2
  •   
  • PD
  •   
  •   
  •   
Pathways, Variants
No phenotype data No genotype data Literature annotations available Not annotated
KCNIP2
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Has annotations
KCNJ11
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ2
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ3
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ4
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ5
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ8
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNK1
  •   
  • PD
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  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNK3
  •   
  • PD
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  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNQ1
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
LMNA
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
PLN
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
RYR2
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
SCN1B
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
SCN2B
  •   
  • PD
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  •   
Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
SCN3B
  •   
  • PD
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  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
SCN4B
  •   
  • PD
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  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Has annotations
SCN5A
  •   
  • PD
  •   
  •   
  •   
Publications, Pathways
No phenotype data No genotype data Literature annotations available Not annotated
SLC8A2
  •   
  • PD
  •   
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  •   
Pathways
No phenotype data No genotype data No literature annotations Not annotated
SLC8A3
  •   
  • PD
  •   
  •   
  •   
Pathways

Non-Curated Information

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

Metabolizing Enzymes

Drug Targets

PharmGKB Curated Pathways

Curated Information

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
warfarin
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  •   
  •   
  •   
Publications

Non-Curated Information

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

Drug Interactions

acenocoumarol Increases the anticoagulant effect
amprenavir The protease inhibitor increases the effect and toxicity of amiodarone
anisindione Increases the anitcoagulant effect
atazanavir Increased risk of cardiotoxicity/arrhythmias
atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
cisapride Increased risk of cardiotoxicity and arrhythmias
clarithromycin Increased risk of cardiotoxicity and arrhythmias
cyclosporine Increases the effect and toxicity of cyclosporine
dicumarol Increases the anticoagulant effect
digoxin Increases the effect of digoxin
dihydroquinidine barbiturate Increases the effect of quinidine
diltiazem Increased risk of cardiotoxicity and arrhythmias
erythromycin Increased risk of cardiotoxicity and arrhythmias
ethotoin Increases the effect of hydantoin
fentanyl Possible bradycardia, hypotension
flecainide Increases the effect and toxicity of flecainide
fosamprenavir The protease inhibitor increases the effect and toxicity of amiodarone
fosphenytoin Increases the effect of hydantoin
gatifloxacin Increased risk of cardiotoxicity and arrhythmias
grepafloxacin Increased risk of cardiotoxicity and arrhythmias
indinavir Indinavir increases the effect and toxicity of amiodarone
iohexol Increased risk of cardiotoxicity and arrhythmias
levofloxacin Increased risk of cardiotoxicity and arrhythmias
mephenytoin Increases the effect of hydantoin
mesoridazine Increased risk of cardiotoxicity and arrhythmias
moxifloxacin Increased risk of cardiotoxicity and arrhythmias
nelfinavir Nelfinavirincreases the effect and toxicity of amiodarone
phenytoin Increases the effect of hydantoin
procainamide Increases serum levels and toxicity of procainamide
quinidine Increases the effect of quinidine
quinidine barbiturate Increases the effect of qiunidine
ranolazine Possible additive effect on QT prolongation
rifampin Rifampin decreases the effect of amiodarone
ritonavir Ritonavir increases the effect and toxicity of amiodarone
saquinavir The protease inhibitor increases the effect and toxicity of amiodarone
simvastatin Increased risk of rhabdomyolysis
sparfloxacin Increased risk of cardiotoxicity and arrhythmias
telithromycin Increased risk of cardiotoxicity and arrhythmias
terfenadine Increased risk of cardiotoxicity and arrhythmias
terfenadine Increased risk of cardiotoxicity and arrhythmias
thioridazine Increased risk of cardiotoxicity and arrhythmias
vardenafil Increased risk of cardiotoxicity and arrhythmias
warfarin Increases the anticoagulant effect
ziprasidone Increased risk of cardiotoxicity and arrhythmias

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
Heart Arrest
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Seizures
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Syncope
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Tachycardia, Ventricular
  •   
  • PD
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Torsades de Pointes
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Ventricular Fibrillation
  •   
  • PD
  •   
  •   
  •   
Publications

Non-Curated Information

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

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

  1. Drug-Induced Long QT Intervals
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • PD
    Submitted by Dan Roden, MD involving ADRB1, ADRB2, KCNE1, KCNE2, KCNH2, KCNQ1, SCN5A, almokalant, amiodarone, amitriptyline, bretylium, bupivacaine, cisapride, disopyramide, dofetilide, encainide, fluconazole, haloperidol, hydroquinidine, isoflurane, itraconazole, ketoconazole, lithium, loratadine, metoclopramide, nortriptyline, procainamide, quinidine, sematilide, sotalol, sulfamethoxazole, thioridazine, trimethoprim, , Long QT Syndrome, Proarrhythmia and Torsades de Pointes
  2. IWPC Warfarin Data Set (NEJM 2009)
    • No genotype data
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • PD
    • PK
    • GN
    Submitted by Warfarin Consortium involving CYP2C9, VKORC1, amiodarone, aspirin, simvastatin, warfarin, and Atrial Fibrillation
  3. mRNA expression levels of PXR splice variants in livers
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • FA
    Submitted by Erin G. Schuetz, PhD involving CYP3A4, NR1I2, , amiodarone, cimetidine, dopamine, erythromycin, ethanol, glucocorticoids, hmg coa reductase inhibitors, midazolam, nicotine, phenobarbital, phenytoin, propofol, thyroid preparations and vasopressin
  4. Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin
    • No genotype data
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • PD
    • PK
    • GN
    Submitted by Brian Gage, MD involving CYP2C9, VKORC1, amiodarone, aspirin, simvastatin, warfarin, , Atrial Fibrillation, post-orthopedic, Pulmonary Embolism, Stroke and Venous Thrombosis

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Genetic Associations in Drug-induced QT Prolongation and Torsades
  2. IWPC Pharmacogenetic Dosing Algorithm
  3. Measured and Predicted Changes in QT Intervals During Atrial Fibrillation
  4. Physicochemical determinants of human renal clearance
  5. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

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LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01118
ChEBI ID:
2663
KEGG Compound ID:
C06823
KEGG Drug ID:
D02910
PubChem Compound ID:
2157
PubChem Substance ID:
159329

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

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

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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