Identification

Name
Amiodarone
Accession Number
DB01118
Description

Amiodarone is a benzofuran derivative, anti-arrhythmic drug used commonly in a variety of settings.4 Most known for its approved indication in life-threatening ventricular arrhythmias, it is also used off-label in the outpatient and inpatient setting for atrial fibrillation. Because of its ability to cause serious toxicity and possibly death, amiodarone use should be reserved for its approved indications, according to prescribing information.18,19,20

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 645.3116
Monoisotopic: 645.023680639
Chemical Formula
C25H29I2NO3
Synonyms
  • 2-Butyl-3-(3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl)benzofuran
  • 2-Butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone
  • 2-n-Butyl-3',5'-diiodo-4'-N-diethylaminoethoxy-3-benzoylbenzofuran
  • Amiodarona
  • Amiodarone
  • Amiodaronum

Pharmacology

Indication

The FDA approved indications for amiodarone are recurrent ventricular fibrillation (VF) and recurrent hemodynamically unstable ventricular tachycardia (VT). The FDA emphasizes that this drug should only be given in these conditions when they are clinically documented and have not responded to normal therapeutic doses of other antiarrhythmic agents, or when other drugs are not tolerated by the patient.18

Off-label indications include atrial fibrillation and supraventricular tachycardia.7,8,9,20

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

After intravenous administration, amiodarone acts to relax smooth muscles that line vascular walls, decreases peripheral vascular resistance (afterload), and increases the cardiac index by a small amount. Administration by this route also decreases cardiac conduction, preventing and treating arrhythmias.2,7,18 When it is given orally, however, amiodarone does not lead to significant changes in the left ventricular ejection fraction. Similar to other anti-arrhythmic agents, controlled clinical trials do not confirm that oral amiodarone increases survival.18

Amiodarone prolongs the QRS duration and QT interval. In addition, a decreased SA (sinoatrial) node automaticity occurs with a decrease in AV node conduction velocity. Ectopic pacemaker automaticity is also inhibited.19 Thyrotoxicosis or hypothyroidism may also result from the administration of amiodarone, which contains high levels of iodine, and interferes with normal thyroid function.11

Mechanism of action

Amiodarone is considered a class III anti-arrhythmic drug. It blocks potassium currents that cause repolarization of the heart muscle during the third phase of the cardiac action potential. As a result amiodarone increases the duration of the action potential as well as the effective refractory period for cardiac cells (myocytes). Therefore, cardiac muscle cell excitability is reduced, preventing and treating abnormal heart rhythms.5,10

Unique from other members of the class III anti-arrhythmic drug class, amiodarone also interferes with the functioning of beta-adrenergic receptors, sodium channels, and calcium channels channels. These actions, at times, can lead to undesirable effects, such as hypotension, bradycardia, and Torsades de pointes (TdP).19 In addition to the above, amiodarone may increase activity of peroxisome proliferator-activated receptors, leading to steatogenic changes in the liver or other organs.14,15 Finally, amiodarone has been found to bind to the thyroid receptor due to its iodine content, potentially leading to amiodarone induced hypothyroidism or thyrotoxicosis.11

TargetActionsOrganism
AHERG human cardiac K+ channel
inhibitor
Humans
ABeta adrenergic receptor
inhibitor
downregulator
Humans
UVoltage-dependent T-type calcium channel subunit alpha-1I
inhibitor
Humans
UVoltage gated L-type calcium channel
inhibitor
Humans
UThyroid hormone receptor
antagonist
binder
Humans and other mammals
UPeroxisome proliferator-activated receptor gamma
agonist
Humans
UPeroxisome proliferator-activated receptor alpha
agonist
Humans
UPeroxisome proliferator-activated receptor gamma coactivator 1-beta
agonist
Humans
Absorption

The Cmax of amiodarone in the plasma is achieved about 3 to 7 hours after administration.18 The general time to onset of action of amiodarone after one dose given by the intravenous route is between 1 and 30 minutes, with therapeutic effects lasting from 1-3 hours. Steady-state concentrations of amiodarone in the plasma ranges between 0.4 to 11.99 μg/ml; it is advisable that steady-state levels are generally maintained between 1.0 and 2.5 μg/ml in patients with arrhythmias.4,5

Interestingly, its onset of action may sometimes begin after 2 to 3 days, but frequently takes 1 to 3 weeks, despite the administration of higher loading doses.18 The bioavailability of amiodarone varies in clinical studies, averaging between 35 and 65%.18

Effect of food

In healthy subjects who were given a single 600-mg dose immediately after consuming a meal high in fat, the AUC of amiodarone increased by 2.3 and the Cmax by 3.8 times.18 Food also enhances absorption, reducing the Tmax by about 37%.18

Volume of distribution

In a pharmacokinetic study of 3 healthy individuals and 3 patients diagnosed with supraventricular tachycardia (SVT), the volume of distribution was found to be 9.26-17.17 L/kg in healthy volunteers and 6.88-21.05 L/kg in the SVT patients.6 Prescribing information mentions that the volume of distribution of amiodarone varies greatly, with a mean distribution of approximately 60 L/kg. It accumulates throughout the body, especially in adipose tissue4 and highly vascular organs including the lung, liver, and spleen. One major metabolite of amiodarone, desethylamiodarone (DEA), is found in even higher proportions in the same tissues as amiodarone.18

Protein binding

The protein binding of amiodarone is about 96%.4,18

Metabolism

This drug is metabolized to the main metabolite desethylamiodarone (DEA)4 by the CYP3A4 and CYP2C8 enzymes. The CYP3A4 enzyme is found in the liver and intestines.18 A hydroxyl metabolite of DEA has been identified in mammals, but its clinical significance is unknown.12

Hover over products below to view reaction partners

Route of elimination

Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion.4 A small amount of desethylamiodarone (DEA) is found in the urine.18

Half-life

The terminal half-life of amiodarone varies according to the patient, but is long nonetheless, and ranges from about 9-100 days. The half-life duration varies according to different sources. 3,7 According to the prescribing information for amiodarone, the average apparent plasma terminal elimination half-life of amiodarone is of 58 days (ranging from 15 to 142 days). The terminal half-life range was between 14 to 75 days for the active metabolite, (DEA).18 The plasma half-life of amiodarone after one dose ranges from 3.2 to 79.7 hours, according to one source.4

Clearance

The clearance of amiodarone after intravenous administration in patients with ventricular fibrillation and ventricular tachycardia ranged from 220 to 440 ml/hr/kg in one clinically study.18 Another study determined that the total body clearance of amiodarone varies from 0.10 to 0.77 L/min after one intravenous dose.4 Renal impairment does not appear to affect the clearance of amiodarone, but hepatic impairment may reduce clearance. Patients with liver cirrhosis exhibited significantly lower Cmax and mean amiodarone concentration for DEA, but not for amiodarone. Severe left ventricular dysfunction prolongs the half-life of DEA.18

A note on monitoring

No guidelines have been developed for adjusting the dose of amiodarone in renal, hepatic, or cardiac abnormalities. In patients on chronic amiodarone treatment, close clinical monitoring is advisable, especially for elderly patients and those with severe left ventricular dysfunction.18

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

The LD50 of oral amiodarone in mice and rats exceeds 3,000 mg/kg.18 An overdose with amiodarone can have a fatal outcome due to its potential to cause arrhythmia. Signs or symptoms of an overdose may include, hypotension, shock, bradycardia, AV block, and liver toxicity. In cases of an overdose, initiate supportive treatment and, if needed, use fluids, vasopressors, or positive inotropic agents. Temporary pacing may be required for heart block. Ensure to monitor liver function regularly. Amiodarone and its main metabolite, DEA, are not removable by dialysis.17

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Amiodarone Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Potassium voltage-gated channel subfamily H member 2MiRP1Not AvailableKCNE2ADR Directly StudiedThe presence of polymorphisms in KCNH2 and KCNE2 may potentially be associated with increased susceptibility to long Q-T syndrome or cardiac arrhytmia when treated with amiodarone.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Amiodarone can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Amiodarone can be increased when combined with Abatacept.
AbirateroneThe metabolism of Amiodarone can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Amiodarone can be decreased when combined with Acalabrutinib.
AcarboseThe risk or severity of hypoglycemia can be increased when Amiodarone is combined with Acarbose.
AcebutololThe therapeutic efficacy of Acebutolol can be increased when used in combination with Amiodarone.
AceclofenacThe risk or severity of hyperkalemia can be increased when Amiodarone is combined with Aceclofenac.
AcemetacinThe risk or severity of hyperkalemia can be increased when Amiodarone is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Amiodarone is combined with Acenocoumarol.
AcetaminophenThe metabolism of Amiodarone can be increased when combined with Acetaminophen.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of amiodarone.
  • Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of amiodarone. Therefore it may reduce the serum concentration and effectiveness of amiodarone.
  • Take with or without food. The absorption is unaffected by food.

Products

Product Ingredients
IngredientUNIICASInChI Key
Amiodarone hydrochloride976728SY6Z19774-82-4ITPDYQOUSLNIHG-UHFFFAOYSA-N
Product Images
International/Other Brands
Amio-Aqueous IV / Aratac / Arycor / Atlansil / Tachyra
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AmiodaroneTabletOralSorres Pharma Inc2009-06-232014-06-20Canada flag
AmiodaroneTabletOralSivem Pharmaceuticals Ulc2012-06-10Not applicableCanada flag
AmiodaroneTabletOralSanis Health Inc2011-06-10Not applicableCanada flag
Amiodarone for Injection 50mg/mlSolutionIntravenousTEVA Canada Limited2004-04-212018-02-23Canada flag
Amiodarone HClInjection, solution1.8 mg/1mLIntravenousCantrell Drug Company2013-10-18Not applicableUS flag
Amiodarone HydrochlorideInjection50 mg/1mLIntravenousAmphastar Pharmaceuticals, Inc.2004-02-112008-01-24US flag
Amiodarone HydrochlorideInjection50 mg/1mLIntravenousAmphastar Pharmaceuticals, Inc.2004-02-112008-01-24US flag
Amiodarone HydrochlorideInjection50 mg/1mLIntravenousAmphastar Pharmaceuticals, Inc.2004-02-112008-01-24US flag
Amiodarone Hydrochloride for InjectionLiquidIntravenousSandoz Canada Incorporated2000-06-14Not applicableCanada flag
Amiodarone Hydrochloride for InjectionSolutionIntravenousPfizer Canada Ulc2002-08-292020-07-10Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Amiodarone HciInjection, solution50 mg/1mLIntravenousHF Acquisition Co LLC, DBA HealthFirst2019-12-08Not applicableUS flag
Amiodarone HClTablet100 mg/1OralMayne Pharma Inc.2017-01-012019-12-31US flag
Amiodarone HClTablet400 mg/1OralCameron Pharmaceuticals, LLC2013-01-01Not applicableUS flag
Amiodarone HClTablet400 mg/1OralMayne Pharma Inc.2013-01-012019-12-31US flag
Amiodarone HClTablet200 mg/1OralCameron Pharmaceuticals, LLC2013-01-01Not applicableUS flag
Amiodarone HClTablet100 mg/1OralCameron Pharmaceuticals, LLC2017-01-01Not applicableUS flag
Amiodarone HClTablet200 mg/1OralMayne Pharma Inc.2013-01-012019-12-31US flag
Amiodarone HydrochlorideInjection, solution50 mg/1mLIntravenousREMEDYREPACK INC.2015-08-182018-05-12US flag
Amiodarone HydrochlorideInjection, solution50 mg/1mLIntravenousMedical Purchasing Solutions, Llc2002-10-14Not applicableUS flag
Amiodarone HydrochlorideInjection, solution50 mg/1mLIntravenousREMEDYREPACK INC.2020-06-19Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Amiodarone HClAmiodarone hydrochloride (1.8 mg/1mL)Injection, solutionIntravenousCantrell Drug Company2013-10-18Not applicableUS flag

Categories

ATC Codes
C01BD01 — Amiodarone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Aryl-phenylketones
Alternative Parents
Benzofurans / Phenoxy compounds / Phenol ethers / Benzoyl derivatives / 3-aroylfurans / Iodobenzenes / Alkyl aryl ethers / Aryl iodides / Heteroaromatic compounds / Trialkylamines
show 5 more
Substituents
3-aroylfuran / Alkyl aryl ether / Amine / Aromatic heteropolycyclic compound / Aryl halide / Aryl iodide / Aryl-phenylketone / Benzenoid / Benzofuran / Benzoyl
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, organoiodine compound, 1-benzofurans, aromatic ketone (CHEBI:2663)

Chemical Identifiers

UNII
N3RQ532IUT
CAS number
1951-25-3
InChI Key
IYIKLHRQXLHMJQ-UHFFFAOYSA-N
InChI
InChI=1S/C25H29I2NO3/c1-4-7-11-22-23(18-10-8-9-12-21(18)31-22)24(29)17-15-19(26)25(20(27)16-17)30-14-13-28(5-2)6-3/h8-10,12,15-16H,4-7,11,13-14H2,1-3H3
IUPAC Name
{2-[4-(2-butyl-1-benzofuran-3-carbonyl)-2,6-diiodophenoxy]ethyl}diethylamine
SMILES
CCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=C(O1)C=CC=C2

References

Synthesis Reference

M.J.A. Walker, P.P.S. Therapeutic Areas I: Central Nervous System, Pain, Metabolic Syndrome, Urology, Gastrointestinal and Cardiovascular: Amiodarone. Comprehensive Medicinal Chemistry II, 2007

US3248401
General References
  1. Singh BN, Vaughan Williams EM: The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmacol. 1970 Aug;39(4):657-67. [PubMed:5485142]
  2. Rosenbaum MB, Chiale PA, Halpern MS, Nau GJ, Przybylski J, Levi RJ, Lazzari JO, Elizari MV: Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol. 1976 Dec;38(7):934-44. [PubMed:793369]
  3. Rosenbaum MB, Chiale PA, Haedo A, Lazzari JO, Elizari MV: Ten years of experience with amiodarone. Am Heart J. 1983 Oct;106(4 Pt 2):957-64. [PubMed:6613843]
  4. Latini R, Tognoni G, Kates RE: Clinical pharmacokinetics of amiodarone. Clin Pharmacokinet. 1984 Mar-Apr;9(2):136-56. doi: 10.2165/00003088-198409020-00002. [PubMed:6370540]
  5. Zipes DP, Prystowsky EN, Heger JJ: Amiodarone: electrophysiologic actions, pharmacokinetics and clinical effects. J Am Coll Cardiol. 1984 Apr;3(4):1059-71. doi: 10.1016/s0735-1097(84)80367-8. [PubMed:6368644]
  6. Riva E, Gerna M, Latini R, Giani P, Volpi A, Maggioni A: Pharmacokinetics of amiodarone in man. J Cardiovasc Pharmacol. 1982 Mar-Apr;4(2):264-9. doi: 10.1097/00005344-198203000-00015. [PubMed:6175810]
  7. Freedman MD, Somberg JC: Pharmacology and pharmacokinetics of amiodarone. J Clin Pharmacol. 1991 Nov;31(11):1061-9. doi: 10.1002/j.1552-4604.1991.tb03673.x. [PubMed:1753010]
  8. Rowland E, Krikler DM: Electrophysiological assessment of amiodarone in treatment of resistant supraventricular arrhythmias. Br Heart J. 1980 Jul;44(1):82-90. doi: 10.1136/hrt.44.1.82. [PubMed:7426165]
  9. Soult JA, Munoz M, Lopez JD, Romero A, Santos J, Tovaruela A: Efficacy and safety of intravenous amiodarone for short-term treatment of paroxysmal supraventricular tachycardia in children. Pediatr Cardiol. 1995 Jan-Feb;16(1):16-9. doi: 10.1007/BF02310328. [PubMed:7753695]
  10. Honjo H, Kodama I, Kamiya K, Toyama J: Block of cardiac sodium channels by amiodarone studied by using Vmax of action potential in single ventricular myocytes. Br J Pharmacol. 1991 Mar;102(3):651-6. doi: 10.1111/j.1476-5381.1991.tb12228.x. [PubMed:1364834]
  11. Narayana SK, Woods DR, Boos CJ: Management of amiodarone-related thyroid problems. Ther Adv Endocrinol Metab. 2011 Jun;2(3):115-26. doi: 10.1177/2042018811398516. [PubMed:23148177]
  12. Ha HR, Bigler L, Binder M, Kozlik P, Stieger B, Hesse M, Altorfer HR, Follath F: Metabolism of amiodarone (part I): identification of a new hydroxylated metabolite of amiodarone. Drug Metab Dispos. 2001 Feb;29(2):152-8. [PubMed:11159805]
  13. Deng P, You T, Chen X, Yuan T, Huang H, Zhong D: Identification of amiodarone metabolites in human bile by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. Drug Metab Dispos. 2011 Jun;39(6):1058-69. doi: 10.1124/dmd.110.037671. Epub 2011 Mar 11. [PubMed:21398391]
  14. Szalowska E, van der Burg B, Man HY, Hendriksen PJ, Peijnenburg AA: Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices. PLoS One. 2014 Jan 29;9(1):e86795. doi: 10.1371/journal.pone.0086795. eCollection 2014. [PubMed:24489787]
  15. Song M, Kim YJ, Ryu JC: Phospholipidosis induced by PPARgamma signaling in human bronchial epithelial (BEAS-2B) cells exposed to amiodarone. Toxicol Sci. 2011 Mar;120(1):98-108. doi: 10.1093/toxsci/kfq361. Epub 2010 Dec 1. [PubMed:21123845]
  16. Electronic Medicines Compendium Amiodarone 100mg Tablets [Link]
  17. Nexterone FDA label [Link]
  18. FDA Approved Drug Products: Cordarone (amiodarone HCl) tablets [Link]
  19. NIH StatPearls: Amiodarone [Link]
  20. AAFP: Medication Guide for Amiodarone [Link]
Human Metabolome Database
HMDB0015250
KEGG Drug
D02910
KEGG Compound
C06823
PubChem Compound
2157
PubChem Substance
46507387
ChemSpider
2072
BindingDB
18957
RxNav
703
ChEBI
2663
ChEMBL
CHEMBL633
ZINC
ZINC000003830212
Therapeutic Targets Database
DAP000496
PharmGKB
PA448383
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
BBI
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Amiodarone
AHFS Codes
  • 24:04.04.20 — Class III Antiarrythmics
PDB Entries
4o8z / 5h4d
MSDS
Download (51.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableParoxysmal Atrial Fibrillation (PAF)1
4CompletedPreventionAtrial Fibrillation (AF)1
4CompletedPreventionAtrial Fibrillation (AF) / Coronary Artery Bypass Grafting (CABG)1
4CompletedPreventionAtrial Fibrillation (AF) / Oesophagectomy1
4CompletedPreventionAtrial Fibrillation (AF) / Surgery, Cardiac1
4CompletedPreventionVentricular Tachycardia (VT)1
4CompletedTreatmentAtrial Fibrillation (AF)2
4CompletedTreatmentAtrial Fibrillation (AF) / Chronic Heart Failure (CHF) / Congestive Cardiomyopathy1
4CompletedTreatmentHeart Failure1
4CompletedTreatmentPersistent Atrial Fibrillation1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Alphapharm Party Ltd.
  • Amerisource Health Services Corp.
  • Amphastar Pharmaceuticals
  • Apotex Inc.
  • APP Pharmaceuticals
  • A-S Medication Solutions LLC
  • Aurolife Pharma LLC
  • Aurosal Pharmaceuticals LLC
  • Barr Pharmaceuticals
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bioniche Pharma
  • Cadila Healthcare Ltd.
  • Cardinal Health
  • Caremark LLC
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • General Injectables and Vaccines Inc.
  • Gland Pharma Ltd.
  • Heartland Repack Services LLC
  • Hikma Pharmaceuticals
  • Hospira Inc.
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Murty Pharmaceuticals Inc.
  • Mylan
  • Neuman Distributors Inc.
  • Novex Pharma
  • Novopharm Ltd.
  • Par Pharmaceuticals
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sagent Pharmaceuticals
  • Sandhills Packaging Inc.
  • Sandoz
  • Sanofi-Aventis Inc.
  • Sicor Pharmaceuticals
  • Spectrum Pharmaceuticals
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Upsher Smith Laboratories
  • Vangard Labs Inc.
  • West-Ward Pharmaceuticals
  • Wockhardt Ltd.
  • Wyeth Pharmaceuticals
  • Zydus Pharmaceuticals
Dosage Forms
FormRouteStrength
Capsule200 MG
Tablet200 MG
Tablet100 MG
TabletOral200 mg
SuspensionOral8 mg/1mL
Injection, solutionParenteral150 MG/3ML
Injection, solutionIntravenous1.8 mg/1mL
Injection, solutionParenteral50 MG/ML
InjectionIntravenous150 mg/3mL
InjectionIntravenous450 mg/9mL
InjectionIntravenous50 mg/1mL
InjectionIntravenous900 mg/18mL
Injection, solutionIntravenous150 mg/3mL
Injection, solutionIntravenous450 mg/9mL
Injection, solutionIntravenous50 mg/1mL
Injection, solutionIntravenous900 mg/18mL
TabletOral200 mg/1
TabletOral300 mg/1
LiquidIntravenous
SolutionIntravenous
SolutionIntravenous150 mg/3ml
Tablet200 mg/1
Tablet
SolutionIntravenous150 mg
Injection, solution, concentrate150 mg/3mL
Injection
Injection, solutionIntravenous1.5 mg/1mL
TabletOral100 mg/1
TabletOral400 mg/1
TabletOral
Prices
Unit descriptionCostUnit
Amiodarone hcl powder38.98USD g
Pacerone 100 mg tablet7.58USD tablet
Pacerone 400 mg tablet7.43USD tablet
Amiodarone hcl 400 mg tablet6.32USD tablet
Cordarone 200 mg tablet4.78USD tablet
Pacerone 200 mg tablet3.53USD tablet
Amiodarone hcl 200 mg tablet3.37USD tablet
Cordarone 200 mg Tablet2.32USD tablet
Apo-Amiodarone 200 mg Tablet1.3USD tablet
Mylan-Amiodarone 200 mg Tablet1.3USD tablet
Novo-Amiodarone 200 mg Tablet1.3USD tablet
Pms-Amiodarone 200 mg Tablet1.3USD tablet
Ratio-Amiodarone 200 mg Tablet1.3USD tablet
Sandoz Amiodarone 200 mg Tablet1.3USD tablet
Amiodarone 150 mg/3 ml vial0.83USD ml
Pms-Amiodarone 100 mg Tablet0.72USD tablet
Amiodarone 900 mg/18 ml vial0.59USD ml
Amiodarone 450 mg/9 ml vial0.57USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5134127No1992-07-282010-01-23US flag
US6869939No2005-03-222022-05-04US flag
US7635773No2009-12-222029-03-13US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)156O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 85. Marly, SA, Belgium.
boiling point (°C)100https://auromedics.com/wordpress/wp-content/uploads/Amiodarone-Hydrochloride-Injection-USP-SDS-US-11-28-17.pdf
water solubilityLowhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018972s042lbl.pdf
logP7.2https://journals.lww.com/md-journal/fulltext/2018/09140/comedication_with_interacting_drugs_predisposes.46.aspx
pKa 6.56 ± 0.06https://www.chemicalbook.com/ChemicalProductProperty_US_CB7131332.aspx
Predicted Properties
PropertyValueSource
Water Solubility0.00476 mg/mLALOGPS
logP7.24ALOGPS
logP7.64ChemAxon
logS-5.1ALOGPS
pKa (Strongest Basic)8.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area42.68 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity145.05 m3·mol-1ChemAxon
Polarizability56.78 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8615
Caco-2 permeable+0.66
P-glycoprotein substrateSubstrate0.8044
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterInhibitor0.5099
CYP450 2C9 substrateNon-substrate0.7959
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.7188
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorInhibitor0.8948
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8615
Ames testNon AMES toxic0.5661
CarcinogenicityNon-carcinogens0.7696
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6539 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5932
hERG inhibition (predictor II)Inhibitor0.7638
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0000009000-8cbab89986761a7a1bc9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0pbj-9300003000-503a542bf1a7678f385e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9110000000-543b8de3c9ba390fa765
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0791000000-77d5d18989052c45b006
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a59-0980000000-a77e32d189cf8e2acdf1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0apl-0940000000-30e016c113387b37ca7c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0000009000-e87a9a6e983c00161beb

Targets

Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...

Components:
References
  1. Wang SP, Wang JA, Luo RH, Cui WY, Wang H: Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation. Clin Exp Pharmacol Physiol. 2008 Sep;35(9):1077-84. doi: 10.1111/j.1440-1681.2008.04964.x. Epub 2008 May 25. [PubMed:18505444]
  2. Varro A, Biliczki P, Iost N, Virag L, Hala O, Kovacs P, Matyus P, Papp JG: Theoretical possibilities for the development of novel antiarrhythmic drugs. Curr Med Chem. 2004 Jan;11(1):1-11. [PubMed:14754422]
  3. Waldhauser KM, Brecht K, Hebeisen S, Ha HR, Konrad D, Bur D, Krahenbuhl S: Interaction with the hERG channel and cytotoxicity of amiodarone and amiodarone analogues. Br J Pharmacol. 2008 Oct;155(4):585-95. doi: 10.1038/bjp.2008.287. Epub 2008 Jul 7. [PubMed:18604229]
  4. FDA Approved Drug Products: Cordarone (amiodarone HCl) tablets [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Downregulator
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...

Components:
References
  1. Drvota V, Haggblad J, Blange I, Magnusson Y, Sylven S: The effect of amiodarone on the beta-adrenergic receptor is due to a downregulation of receptor protein and not to a receptor-ligand interaction. Biochem Biophys Res Commun. 1999 Feb 16;255(2):515-20. doi: 10.1006/bbrc.1998.0138. [PubMed:10049740]
  2. Disatnik MH, Shainberg A: Regulation of beta-adrenoceptors by thyroid hormone and amiodarone in rat myocardiac cells in culture. Biochem Pharmacol. 1991 Mar 15-Apr 1;41(6-7):1039-44. doi: 10.1016/0006-2952(91)90212-n. [PubMed:1672592]
  3. FDA Approved Drug Products: Cordarone (amiodarone HCl) tablets [Link]
  4. NIH StatPearls: Amiodarone [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1I
Uniprot ID
Q9P0X4
Uniprot Name
Voltage-dependent T-type calcium channel subunit alpha-1I
Molecular Weight
245100.8 Da
References
  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [PubMed:1281221]
  2. Lewalter T, Pittrow D, Goette A, Kirch W, Hohnloser S: [Clinical pharmacology and electrophysiological properties of dronedarone]. Dtsch Med Wochenschr. 2010 Mar;135 Suppl 2:S43-7. doi: 10.1055/s-0030-1249208. Epub 2010 Mar 10. [PubMed:20221978]
  3. Lubic SP, Nguyen KP, Dave B, Giacomini JC: Antiarrhythmic agent amiodarone possesses calcium channel blocker properties. J Cardiovasc Pharmacol. 1994 Nov;24(5):707-14. doi: 10.1097/00005344-199424050-00004. [PubMed:7532747]
  4. NIH StatPearls: Amiodarone [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...

Components:
References
  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [PubMed:1281221]
  2. Lewalter T, Pittrow D, Goette A, Kirch W, Hohnloser S: [Clinical pharmacology and electrophysiological properties of dronedarone]. Dtsch Med Wochenschr. 2010 Mar;135 Suppl 2:S43-7. doi: 10.1055/s-0030-1249208. Epub 2010 Mar 10. [PubMed:20221978]
  3. Lubic SP, Nguyen KP, Dave B, Giacomini JC: Antiarrhythmic agent amiodarone possesses calcium channel blocker properties. J Cardiovasc Pharmacol. 1994 Nov;24(5):707-14. doi: 10.1097/00005344-199424050-00004. [PubMed:7532747]
  4. Watanabe Y, Kimura J: Inhibitory effect of amiodarone on Na(+)/Ca(2+) exchange current in guinea-pig cardiac myocytes. Br J Pharmacol. 2000 Sep;131(1):80-4. doi: 10.1038/sj.bjp.0703527. [PubMed:10960072]
  5. NIH StatPearls: Amiodarone [Link]
Kind
Protein group
Organism
Humans and other mammals
Pharmacological action
Unknown
Actions
Antagonist
Binder
General Function
Zinc ion binding
Specific Function
Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.Isoform Al...

Components:
References
  1. Carlsson B, Singh BN, Temciuc M, Nilsson S, Li YL, Mellin C, Malm J: Synthesis and preliminary characterization of a novel antiarrhythmic compound (KB130015) with an improved toxicity profile compared with amiodarone. J Med Chem. 2002 Jan 31;45(3):623-30. [PubMed:11806713]
  2. Norman MF, Lavin TN: Antagonism of thyroid hormone action by amiodarone in rat pituitary tumor cells. J Clin Invest. 1989 Jan;83(1):306-13. doi: 10.1172/JCI113874. [PubMed:2910914]
  3. Narayana SK, Woods DR, Boos CJ: Management of amiodarone-related thyroid problems. Ther Adv Endocrinol Metab. 2011 Jun;2(3):115-26. doi: 10.1177/2042018811398516. [PubMed:23148177]
  4. NIH StatPearls: Amiodarone [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Szalowska E, van der Burg B, Man HY, Hendriksen PJ, Peijnenburg AA: Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices. PLoS One. 2014 Jan 29;9(1):e86795. doi: 10.1371/journal.pone.0086795. eCollection 2014. [PubMed:24489787]
  2. Song M, Kim YJ, Ryu JC: Phospholipidosis induced by PPARgamma signaling in human bronchial epithelial (BEAS-2B) cells exposed to amiodarone. Toxicol Sci. 2011 Mar;120(1):98-108. doi: 10.1093/toxsci/kfq361. Epub 2010 Dec 1. [PubMed:21123845]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
References
  1. Szalowska E, van der Burg B, Man HY, Hendriksen PJ, Peijnenburg AA: Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices. PLoS One. 2014 Jan 29;9(1):e86795. doi: 10.1371/journal.pone.0086795. eCollection 2014. [PubMed:24489787]
  2. McCarthy TC, Pollak PT, Hanniman EA, Sinal CJ: Disruption of hepatic lipid homeostasis in mice after amiodarone treatment is associated with peroxisome proliferator-activated receptor-alpha target gene activation. J Pharmacol Exp Ther. 2004 Dec;311(3):864-73. doi: 10.1124/jpet.104.072785. Epub 2004 Jul 20. [PubMed:15265979]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Plays a role of stimulator of transcription factors and nuclear receptors activities. Activates transcriptional activity of estrogen receptor alpha, nuclear respiratory factor 1 (NRF1) and glucocorticoid receptor in the presence of glucocorticoids. May play a role in constitutive non-adrenergic-mediated mitochondrial biogenesis as suggested by increased basal oxygen consumption and mitochondrial number when overexpressed. May be involved in fat oxidation and non-oxidative glucose metabolism and in the regulation of energy expenditure. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner.
Specific Function
Af-2 domain binding
Gene Name
PPARGC1B
Uniprot ID
Q86YN6
Uniprot Name
Peroxisome proliferator-activated receptor gamma coactivator 1-beta
Molecular Weight
113221.09 Da
References
  1. Szalowska E, van der Burg B, Man HY, Hendriksen PJ, Peijnenburg AA: Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices. PLoS One. 2014 Jan 29;9(1):e86795. doi: 10.1371/journal.pone.0086795. eCollection 2014. [PubMed:24489787]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
Inhibitor
Curator comments
Amiodarone competitively inhibits the CYP3A4 as it is a substrate of this enzyme.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Elsherbiny ME, El-Kadi AO, Brocks DR: The metabolism of amiodarone by various CYP isoenzymes of human and rat, and the inhibitory influence of ketoconazole. J Pharm Pharm Sci. 2008;11(1):147-59. [PubMed:18445370]
  3. Ohyama K, Nakajima M, Nakamura S, Shimada N, Yamazaki H, Yokoi T: A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor. Drug Metab Dispos. 2000 Nov;28(11):1303-10. [PubMed:11038157]
  4. Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Br J Clin Pharmacol. 2000 Mar;49(3):244-53. doi: 10.1046/j.1365-2125.2000.00134.x. [PubMed:10718780]
  5. Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L53). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
  6. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  7. Electronic Medicines Compendium Amiodarone 100mg Tablets [Link]
  8. FDA Approved Drug Products: Cordarone (amiodarone HCl) tablets [Link]
  9. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Ohyama K, Nakajima M, Nakamura S, Shimada N, Yamazaki H, Yokoi T: A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor. Drug Metab Dispos. 2000 Nov;28(11):1303-10. [PubMed:11038157]
  3. Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L53). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
  4. FDA Approved Drug Products: Cordarone (amiodarone HCl) tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Yamreudeewong W, DeBisschop M, Martin LG, Lower DL: Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Saf. 2003;26(6):421-38. doi: 10.2165/00002018-200326060-00004. [PubMed:12688833]
  3. Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Br J Clin Pharmacol. 2000 Mar;49(3):244-53. doi: 10.1046/j.1365-2125.2000.00134.x. [PubMed:10718780]
  4. Fukumoto K, Kobayashi T, Tachibana K, Kato R, Tanaka K, Komamura K, Kamakura S, Kitakaze M, Ueno K: Effect of amiodarone on the serum concentration/dose ratio of metoprolol in patients with cardiac arrhythmia. Drug Metab Pharmacokinet. 2006 Dec;21(6):501-5. [PubMed:17220566]
  5. Jaruratanasirikul S, Hortiwakul R: The inhibitory effect of amiodarone and desethylamiodarone on dextromethorphan O-demethylation in human and rat liver microsomes. J Pharm Pharmacol. 1994 Nov;46(11):933-5. doi: 10.1111/j.2042-7158.1994.tb05721.x. [PubMed:7897605]
  6. Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L53). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
  7. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  8. Flockhart Table of Drug Interactions [Link]
  9. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Yamreudeewong W, DeBisschop M, Martin LG, Lower DL: Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Saf. 2003;26(6):421-38. doi: 10.2165/00002018-200326060-00004. [PubMed:12688833]
  3. Naganuma M, Shiga T, Nishikata K, Tsuchiya T, Kasanuki H, Fujii E: Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy. J Cardiovasc Pharmacol Ther. 2001 Oct;6(4):363-7. doi: 10.1177/107424840100600405. [PubMed:11907638]
  4. Heimark LD, Wienkers L, Kunze K, Gibaldi M, Eddy AC, Trager WF, O'Reilly RA, Goulart DA: The mechanism of the interaction between amiodarone and warfarin in humans. Clin Pharmacol Ther. 1992 Apr;51(4):398-407. [PubMed:1563209]
  5. Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L53). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
  6. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  7. Drug Interactions & Labeling - FDA [Link]
  8. Flockhart Table of Drug Interactions [Link]
  9. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
The induction of p-gp by glycoprotein is only supported by data from in vitro studies. Clinical relevance is unknown.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Naganuma M, Shiga T, Nishikata K, Tsuchiya T, Kasanuki H, Fujii E: Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy. J Cardiovasc Pharmacol Ther. 2001 Oct;6(4):363-7. doi: 10.1177/107424840100600405. [PubMed:11907638]
  2. McDonald MG, Au NT, Rettie AE: P450-Based Drug-Drug Interactions of Amiodarone and its Metabolites: Diversity of Inhibitory Mechanisms. Drug Metab Dispos. 2015 Nov;43(11):1661-9. doi: 10.1124/dmd.115.065623. Epub 2015 Aug 21. [PubMed:26296708]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  4. Flockhart Table of Drug Interactions [Link]
  5. FDA Approved Drug Products: Cordarone (amiodarone HCl) tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
CYP2C19 plays a minor role in amiodarone metabolism and is unlikely to cause clinically significant interaction.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Ohyama K, Nakajima M, Nakamura S, Shimada N, Yamazaki H, Yokoi T: A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor. Drug Metab Dispos. 2000 Nov;28(11):1303-10. [PubMed:11038157]
  2. Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Br J Clin Pharmacol. 2000 Mar;49(3):244-53. doi: 10.1046/j.1365-2125.2000.00134.x. [PubMed:10718780]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Elsherbiny ME, El-Kadi AO, Brocks DR: The metabolism of amiodarone by various CYP isoenzymes of human and rat, and the inhibitory influence of ketoconazole. J Pharm Pharm Sci. 2008;11(1):147-59. [PubMed:18445370]
  2. Wu Q, Ning B, Xuan J, Ren Z, Guo L, Bryant MS: The role of CYP 3A4 and 1A1 in amiodarone-induced hepatocellular toxicity. Toxicol Lett. 2016 Jun 24;253:55-62. doi: 10.1016/j.toxlet.2016.04.016. Epub 2016 Apr 22. [PubMed:27113703]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data regarding this enzyme action are limited in the literature.
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Br J Clin Pharmacol. 2000 Mar;49(3):244-53. doi: 10.1046/j.1365-2125.2000.00134.x. [PubMed:10718780]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible f...
Gene Name
CYP2J2
Uniprot ID
P51589
Uniprot Name
Cytochrome P450 2J2
Molecular Weight
57610.165 Da
References
  1. Karkhanis A, Lam HY, Venkatesan G, Koh SK, Chai CL, Zhou L, Hong Y, Kojodjojo P, Chan EC: Multiple modes of inhibition of human cytochrome P450 2J2 by dronedarone, amiodarone and their active metabolites. Biochem Pharmacol. 2016 May 1;107:67-80. doi: 10.1016/j.bcp.2016.03.005. Epub 2016 Mar 10. [PubMed:26972388]
  2. Karkhanis A, Tram NDT, Chan ECY: Effects of dronedarone, amiodarone and their active metabolites on sequential metabolism of arachidonic acid to epoxyeicosatrienoic and dihydroxyeicosatrienoic acids. Biochem Pharmacol. 2017 Dec 15;146:188-198. doi: 10.1016/j.bcp.2017.09.012. Epub 2017 Sep 25. [PubMed:28958841]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Veronese ME, McLean S, Hendriks R: Plasma protein binding of amiodarone in a patient population: measurement by erythrocyte partitioning and a novel glass-binding method. Br J Clin Pharmacol. 1988 Dec;26(6):721-31. doi: 10.1111/j.1365-2125.1988.tb05311.x. [PubMed:3242577]
  2. Neyroz P, Bonati M: In vitro amiodarone protein binding and its interaction with warfarin. Experientia. 1985 Mar 15;41(3):361-3. doi: 10.1007/bf02004505. [PubMed:3972082]
  3. Lalloz MR, Byfield PG, Greenwood RM, Himsworth RL: Binding of amiodarone by serum proteins and the effects of drugs, hormones and other interacting ligands. J Pharm Pharmacol. 1984 Jun;36(6):366-72. doi: 10.1111/j.2042-7158.1984.tb04400.x. [PubMed:6146666]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
The induction of p-glycoprotein by amiodarone is only supported by in vitro data. Clinical relevance is unknown.
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Schuetz EG, Beck WT, Schuetz JD: Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol. 1996 Feb;49(2):311-8. [PubMed:8632764]
  2. Katoh M, Nakajima M, Yamazaki H, Yokoi T: Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport. Eur J Pharm Sci. 2001 Feb;12(4):505-13. [PubMed:11231118]
  3. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. [PubMed:12235267]
  4. Tiberghien F, Loor F: Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. Anticancer Drugs. 1996 Jul;7(5):568-78. [PubMed:8862725]
  5. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR: Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999 Mar;16(3):408-14. [PubMed:10213372]
  6. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Curator comments
There are limited data in the literature to support this transporter action. It is not likely to be clinically significant.
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Electronic Medicines Compendium Amiodarone 100mg Tablets [Link]
  2. FDA Approved Drug Products: Cordarone (amiodarone HCl) tablets [Link]

Drug created on June 13, 2005 07:24 / Updated on October 23, 2020 21:53

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates