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]
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 (source: Drug Bank)

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. (source: Drug Bank)

ATC Therapeutic Category

  • C01BD:Antiarrhythmics, class III

Pharmacology, Interactions, and Contraindications

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. (source: Drug Bank)

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. (source: Drug Bank)

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. (source: Drug Bank)

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. (source: Drug Bank)

Protein Binding

>96% (source: Drug Bank)

Absorption

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

Toxicity

Intravenous, mouse: LD<sub>50</sub> = 178 mg/kg. Some side effects have a significant mortality rate: specifically, hepatitis, exacerbation of asthma and congestive failure, and pneumonitis. (source: Drug Bank)

Isomeric SMILES Code:

CCCCc1c(c2ccccc2o1)C(=O)c3cc(c(c(c3)I)OCCN(CC)CC)I (source: Drug Bank)

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.

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
  •   
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
CALU
  • CO
  •   
  • PK
  •   
  • GN
Publications
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
  • CO
  •   
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  •   
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
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
KCNH2
  •   
  •   
  •   
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
SCN5A
  •   
  • PD
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
VKORC1
  • CO
  •   
  • PK
  •   
  • GN
Publications

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

Drug Targets

Gene Description
ADRA1A Uncurated Annotation (source: Drug Bank)
ADRB1 Uncurated Annotation (source: Drug Bank)
KCNH2 Uncurated Annotation (source: Drug Bank)

PharmGKB Curated Pathways

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
  •   
  • PD
  •   
  •   
  •   
Publications

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

Drug Interactions

Drug Description
acenocoumarol Uncurated Annotation Increases the anticoagulant effect (source: Drug Bank)
amprenavir Uncurated Annotation The protease inhibitor increases the effect and toxicity of amiodarone (source: Drug Bank)
anisindione Uncurated Annotation Increases the anitcoagulant effect (source: Drug Bank)
atazanavir Uncurated Annotation Increased risk of cardiotoxicity/arrhythmias (source: Drug Bank)
atomoxetine Uncurated Annotation The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine (source: Drug Bank)
cisapride Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clarithromycin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
cyclosporine Uncurated Annotation Increases the effect and toxicity of cyclosporine (source: Drug Bank)
dicumarol Uncurated Annotation Increases the anticoagulant effect (source: Drug Bank)
digoxin Uncurated Annotation Increases the effect of digoxin (source: Drug Bank)
diltiazem Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
erythromycin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
ethotoin Uncurated Annotation Increases the effect of hydantoin (source: Drug Bank)
fentanyl Uncurated Annotation Possible bradycardia, hypotension (source: Drug Bank)
flecainide Uncurated Annotation Increases the effect and toxicity of flecainide (source: Drug Bank)
fosamprenavir Uncurated Annotation The protease inhibitor increases the effect and toxicity of amiodarone (source: Drug Bank)
fosphenytoin Uncurated Annotation Increases the effect of hydantoin (source: Drug Bank)
gatifloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
grepafloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
indinavir Uncurated Annotation Indinavir increases the effect and toxicity of amiodarone (source: Drug Bank)
iohexol Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
levofloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
mephenytoin Uncurated Annotation Increases the effect of hydantoin (source: Drug Bank)
mesoridazine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
moxifloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
nelfinavir Uncurated Annotation Nelfinavirincreases the effect and toxicity of amiodarone (source: Drug Bank)
phenytoin Uncurated Annotation Increases the effect of hydantoin (source: Drug Bank)
procainamide Uncurated Annotation Increases serum levels and toxicity of procainamide (source: Drug Bank)
quinidine Uncurated Annotation Increases the effect of quinidine (source: Drug Bank)
quinidine Uncurated Annotation Increases the effect of qiunidine (source: Drug Bank)
ranolazine Uncurated Annotation Possible additive effect on QT prolongation (source: Drug Bank)
rifampin Uncurated Annotation Rifampin decreases the effect of amiodarone (source: Drug Bank)
ritonavir Uncurated Annotation Ritonavir increases the effect and toxicity of amiodarone (source: Drug Bank)
saquinavir Uncurated Annotation The protease inhibitor increases the effect and toxicity of amiodarone (source: Drug Bank)
simvastatin Uncurated Annotation Increased risk of rhabdomyolysis (source: Drug Bank)
sparfloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
telithromycin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
terfenadine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
terfenadine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
thioridazine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
vardenafil Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
warfarin Uncurated Annotation Increases the anticoagulant effect (source: Drug Bank)
ziprasidone Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (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
Heart Arrest
  •   
  • PD
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Long QT Syndrome
  •   
  •   
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
Pulmonary Embolism
  • CO
  •   
  • PK
  •   
  • GN
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
Phenotype data available No genotype data Literature annotations available Not annotated
Venous Thrombosis
  • CO
  •   
  • PK
  •   
  • GN
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. ITPC Ethnicity Data Set, 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. 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
  4. 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
  5. 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

Downloads

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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
IUPHAR Ligand ID:
2566

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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