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Identification
NameAmiodarone
Accession NumberDB01118  (APRD00288)
TypeSmall Molecule
GroupsApproved, Investigational
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]

Structure
Thumb
Synonyms
SynonymLanguageCode
2-Butyl-3-(3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl)benzofuranNot AvailableNot Available
2-Butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketoneNot AvailableNot Available
2-N-Butyl-3',5'-diiodo-4'-N-diethylaminoethoxy-3-benzoylbenzofuranNot AvailableNot Available
AmiodaronaSpanishINN
AmiodaroneNot AvailableNot Available
AmiodaronumLatinINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cordaronetablet200 mgoralWyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.1985-12-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Nexteroneinjection, solution1.5 mg/mLintravenousBaxter Healthcare Corporation2010-11-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Nexteroneinjection, solution1.8 mg/mLintravenousBaxter Healthcare Corporation2010-11-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Cordaronetablet200 mgoralPfizer Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amiodarone Hydrochloridetablet200 mgoralTeva Pharmaceuticals USA Inc1998-11-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection, solution50 mg/mLintravenousWest ward Pharmaceutical Corp2008-02-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralEon Labs, Inc.1998-12-23Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paceronetablet100 mgoralUpsher Smith Laboratories, Inc.2011-01-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paceronetablet400 mgoralUpsher Smith Laboratories, Inc.2000-06-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paceronetablet200 mgoralUpsher Smith Laboratories, Inc.2011-01-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection, solution50 mg/mLintravenousHospira, Inc.2013-11-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection, solution50 mg/mLintravenousHospira, Inc.2013-11-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection, solution50 mg/mLintravenousHospira, Inc.2002-10-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralNcs Health Care Of Ky, Inc Dba Vangard Labs1998-12-23Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralRebel Distributors Corp2009-08-10Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection, solution50 mg/mLintravenousSagent Pharmaceuticals2013-07-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralREMEDYREPACK INC.2011-04-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralMylan Institutional Inc.2007-08-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralTaro Pharmaceuticals U.S.A., Inc.2001-03-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet100 mgoralTaro Pharmaceuticals U.S.A., Inc.2001-03-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet400 mgoralTaro Pharmaceuticals U.S.A., Inc.2002-11-29Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralREMEDYREPACK INC.2014-08-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection, solution50 mg/mLintravenousGeneral Injectables & Vaccines, Inc2012-06-06Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection, solution, concentrate50 mg/mLintravenousGeneral Injectables & Vaccines, Inc.2010-03-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection50 mg/mLintravenousGENERAL INJECTABLES AND VACCINES, INC.2014-09-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralState of Florida DOH Central Pharmacy2014-11-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralPhysicians Total Care, Inc.2002-04-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paceronetablet200 mgoralPhysicians Total Care, Inc.2008-10-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection, solution50 mg/mLintravenousPhysicians Total Care, Inc.2006-12-11Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralCardinal Health2009-09-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralCardinal Health1998-11-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paceronetablet200 mgoralCardinal Health2011-01-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection50 mg/mLintravenousWockhardt Limited2008-10-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection50 mg/mLintravenousWockhardt Limited2008-10-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralGolden State Medical Supply, Inc.2001-03-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralApotex Corp2008-11-06Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection, solution50 mg/mLintravenousAPP Pharmaceuticals, LLC2003-01-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralMc Kesson Packaging A Business Unit Of Mc Kesson Corporation2008-03-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paceronetablet200 mgoralRx Pak Division Of Mc Kesson Corporation2014-04-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralCadila Healthcare Limited2009-08-10Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochlorideinjection, solution50 mg/mLintravenousMylan Institutional LLC2002-10-14Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paceronetablet200 mgoralAphena Pharma Solutions Tennessee, Llc2011-01-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralAmerican Health Packaging2009-09-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralZydus Pharmaceuticals (USA) Inc.2009-08-10Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodarone Hydrochloridetablet200 mgoralMc Kesson Contract Packaging2012-01-03Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Amiodaronetablet200 mgoralSanis Health IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Amiodaronetablet200 mgoralSivem Pharmaceuticals UlcNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Over the Counter ProductsNot Available
International Brands
NameCompany
Amio-Aqueous IVNot Available
AratacNot Available
ArycorNot Available
AtlansilNot Available
TachyraNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Amiodarone Hydrochloride
Thumb
  • InChI Key: ITPDYQOUSLNIHG-UHFFFAOYSA-N
  • Monoisotopic Mass: 681.000358378
  • Average Mass: 681.773
DBSALT000355
Categories
CAS number1951-25-3
WeightAverage: 645.3116
Monoisotopic: 645.023680639
Chemical FormulaC25H29I2NO3
InChI KeyIYIKLHRQXLHMJQ-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=CC=CC=C2O1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzofurans. These are organic compounds containing a benzene ring fused to a furan. Furan is a five-membered aromatic ring with four carbon atoms and one oxygen atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzofurans
Sub ClassNot Available
Direct ParentBenzofurans
Alternative Parents
Substituents
  • Benzofuran
  • Acetophenone
  • Aryl ketone
  • 3-aroylfuran
  • Phenol ether
  • Benzoyl
  • Iodobenzene
  • Halobenzene
  • Alkyl aryl ether
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl iodide
  • Aryl halide
  • Heteroaromatic compound
  • Furan
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ketone
  • Oxacycle
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organoiodide
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationIntravenously, 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.
PharmacodynamicsAmiodarone 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.
Mechanism of actionThe 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.
AbsorptionSlow and variable (about 20 to 55% of an oral dose is absorbed).
Volume of distributionNot Available
Protein binding>96%
Metabolism

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.

SubstrateEnzymesProduct
Amiodarone
N-desethylamiodaroneDetails
Route of eliminationAmiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine.
Half life58 days (range 15-142 days)
Clearance
  • 90-158 mL/h/kg [Healthy with a single dose IV (5 mg/kg over 15 min)]
  • 100 mL/h/kg [Normal subjects > 65 yrs]
  • 150 mL/h/kg [younger subjects]
  • 220 and 440 mL/h/kg [patients with VT and VF]
ToxicityIntravenous, mouse: LD50 = 178 mg/kg. Some side effects have a significant mortality rate: specifically, hepatitis, exacerbation of asthma and congestive failure, and pneumonitis.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Amiodarone Action PathwayDrug actionSMP00665
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Potassium voltage-gated channel subfamily H member 2
Gene symbol: KCNH2
UniProt: Q12809
Not AvailableMiRP1KCNE2Channels formed with mutant MiRP1 subunits and HERG showed slower activation, faster deactivation, and increased drug sensitivity and is associated with cardiac arrhythmia.10219239
ADMET
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 substrateInhibitor0.8948
CYP450 2D6 substrateInhibitor0.8931
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateNon-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
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injectionintravenous50 mg/mL
Injection, solutionintravenous1.5 mg/mL
Injection, solutionintravenous1.8 mg/mL
Injection, solutionintravenous50 mg/mL
Injection, solution, concentrateintravenous50 mg/mL
Tabletoral100 mg
Tabletoral200 mg
Tabletoral400 mg
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
CountryPatent NumberApprovedExpires (estimated)
United States51341271993-01-232010-01-23
United States76357732009-03-132029-03-13
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point156Tondeur, R. and Binon, F.; U.S. Patent 3,248,401; April 26,1966; assigned to Societe Beige de I'Azote et des Produits Chimiques du Marly, SA, Belgium.
water solubilityLowNot Available
logP7.57AVDEEF,A (1997)
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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US3248401
General Reference
  1. DELTOUR G, BINON F, TONDEUR R, GOLDENBERG C, HENAUX F, SION R, DERAY E, CHARLIER R: [Studies in the benzofuran series. VI. Coronary-dilating activity of alkylated and aminoalkylated derivatives of 3-benzoylbenzofuran.] Arch Int Pharmacodyn Ther. 1962 Sep 1;139:247-54. Pubmed
  2. CHARLIER R, DELTOUR G, TONDEUR R, BINON F: [Studies in the benzofuran series. VII. Preliminary pharmacological study of 2-butyl-3-(3,5-diiodo-4-beta-N-diethylaminoethoxybenzoyl)-benzofuran.] Arch Int Pharmacodyn Ther. 1962 Sep 1;139:255-64. Pubmed
  3. 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
  4. 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
  5. 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
External Links
ATC CodesC01BD01
AHFS Codes
  • 24:04.04.20
PDB EntriesNot Available
FDA labelDownload (545 KB)
MSDSDownload (51.8 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolAmiodarone may increase the anticoagulant effect of acenocoumarol.
AlvimopanDecreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
AmprenavirThe protease inhibitor, amprenavir, may increase the effect and toxicity of amiodarone.
AnisindioneAmiodarone may increase the anticoagulant effect of anisindione.
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
AtazanavirIncreased risk of cardiotoxicity and arrhythmias.
AtomoxetineThe CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
CisaprideIncreased risk of cardiotoxicity and arrhythmias
ClarithromycinIncreased risk of cardiotoxicity and arrhythmias
ColesevelamBile Acid Sequestrants may decrease the bioavailability of Amiodarone. Consider alternative antilipemic agent. The risk of subtherapeutic amiodarone serum concentrations when such is being used for the treatment of malignant arrhythmias can be very large. The effect (ie, reduced risk) of separating doses of these agents is unknown. Amiodarone should be administered at least 1 hour before or 4 hours after colesevelam.1 Similar dosing with other agents seems warranted.
CyclosporineAmiodarone may increase the therapeutic and adverse effects of cyclosporine.
Dabigatran etexilateAmiodarone may increase the serum concentration of dabigatran etexilate, resulting in increased risk of bleeding. Consider modifying therapy.
DicoumarolAmiodarone may increase the anticoagulant effect of dicumarol.
DigoxinAmiodarone may increase the effect of digoxin.
Dihydroquinidine barbiturateIncreases the effect of quinidine
DiltiazemIncreased risk of cardiotoxicity and arrhythmias
EltrombopagAffects hepatic enzyme CYP2C9/10 metabolism, increases effect/level of eltrombopag.
ErythromycinIncreased risk of cardiotoxicity and arrhythmias
EthotoinIncreases the effect of hydantoin
EtravirineAmiodarone, when used concomitantly with etravirine, may decrease in serum concentration. If possible, monitoring for decreased amiodarone levels is recommended.
EtravirineAmiodarone, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. If possible, monitoring of amiodarone levels is recommended.
FentanylPossible bradycardia, hypotension
FingolimodPharmacodynamic synergist. Contraindicated. Increased risk of bradycardia, AV block, and torsade de pointes.
FlecainideAmiodarone may increase the effect and toxicity of flecainide
FosamprenavirThe protease inhibitor, fosamprenavir, may increase the effect and toxicity of amiodarone.
FosphenytoinAmiodarone may increase the effect of fosphenytoin.
GatifloxacinIncreased risk of cardiotoxicity and arrhythmias
GrepafloxacinIncreased risk of cardiotoxicity and arrhythmias
IndacaterolConcomitant therapy with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs that prolong the QTc interval should be monitored closely. These drugs may potentiate the effect of adrenergic agonist on the cardiovascular system.
IndinavirIndinavir increases the effect and toxicity of amiodarone
IohexolIncreased risk of cardiotoxicity and arrhythmias
LevofloxacinIncreased risk of cardiotoxicity and arrhythmias
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MephenytoinIncreases the effect of hydantoin
MesoridazineIncreased risk of cardiotoxicity and arrhythmias
MoxifloxacinIncreased risk of cardiotoxicity and arrhythmias
NelfinavirNelfinavir may increase the effect and toxicity of amiodarone.
PhenytoinAmiodarone may increase the therapeutic and adverse effects of phenytoin.
ProcainamideAmiodarone may increase serum levels and toxicity of procainamide.
QuinidineAmiodarone may increase the effect of quinidine.
Quinidine barbiturateIncreases the effect of qiunidine
RanolazinePossible additive effect on QT prolongation
RifampicinRifampin decreases the effect of amiodarone
RitonavirRitonavir increases the effect and toxicity of amiodarone
RoflumilastIncreases roflumilast levels.
SaquinavirThe protease inhibitor, saquinavir, may increase the effect and toxicity of amiodarone.
SimvastatinIncreased risk of rhabdomyolysis
SparfloxacinIncreased risk of cardiotoxicity and arrhythmias
TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
TamoxifenAmiodarone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
TamsulosinAmiodarone, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Amiodarone is initiated, discontinued, or dose changed.
TelavancinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
TelithromycinTelithromycin may reduce clearance of Amiodarone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Amiodarone if Telithromycin is initiated, discontinued or dose changed.
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
ThioridazineIncreased risk of cardiotoxicity and arrhythmias
ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
TipranavirTipranavir, co-administered with Ritonavir, may increase the plasma concentration of Amiodarone. Concomitant therapy is contraindicated.
TizanidineAmiodarone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
TolterodineAmiodarone may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
TopotecanThe p-glycoprotein inhibitor, Amiodarone, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
ToremifeneAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
TramadolAmiodarone may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Amiodarone may decrease the effect of Tramadol by decreasing active metabolite production.
TrazodoneThe CYP3A4 inhibitor, Amiodarone, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Amiodarone is initiated, discontinued or dose changed.
TrimipramineAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
VardenafilIncreased risk of cardiotoxicity and arrhythmias
VerapamilAdditive bradycardic effects may occur. One case report of sinus arrest has been reported. Monitor for changes in the therapeutic effect and signs of Verapamil toxicity if Amiodarone is initiated, discontinued or dose changed.
VoriconazoleAdditive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of amiodarone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of amiodarone if voriconazole is initiated, discontinued or dose changed.
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
WarfarinAmiodarone may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if amiodarone is initiated, discontinued or dose changed.
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
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.

Targets

1. Potassium voltage-gated channel subfamily H member 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily H member 2 Q12809 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. 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. Epub 2008 May 25. Pubmed
  3. 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
  4. 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. Epub 2008 Jul 7. Pubmed

2. Beta-1 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Beta-1 adrenergic receptor P08588 Details

References:

  1. Doggrell SA, Brown L: Present and future pharmacotherapy for heart failure. Expert Opin Pharmacother. 2002 Jul;3(7):915-30. Pubmed

3. Voltage-dependent T-type calcium channel subunit alpha-1H

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent T-type calcium channel subunit alpha-1H O95180 Details

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
  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. Epub 2010 Mar 10. Pubmed

4. Voltage-dependent calcium channel subunit alpha-2/delta-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent calcium channel subunit alpha-2/delta-2 Q9NY47 Details

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
  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. Epub 2010 Mar 10. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. 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

2. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

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
  2. Information Hyperlinked Over Proteins (iHOP) – Website
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. 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

3. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

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
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

9. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

10. Cytochrome P450 2A6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2A6 P11509 Details

References:

  1. Lexicomp

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor inducer

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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
  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
  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
  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
  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

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:22