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Details

Stereochemistry ACHIRAL
Molecular Formula C25H29I2NO3
Molecular Weight 645.3125
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMIODARONE

SMILES

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

InChI

InChIKey=IYIKLHRQXLHMJQ-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: https://www.drugs.com/pro/amiodarone.html | DOI: 10.1007/978-1-4613-2827-8_26

Amiodarone is an antiarrhythmic with mainly class III properties, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes. Like class I drugs, amiodarone blocks sodium channels at rapid pacing frequencies, and like class II drugs, amiodarone exerts a noncompetitive antisympathetic action. In addition to blocking sodium channels, amiodarone blocks myocardial potassium channels, which contributes to slowing of conduction and prolongation of refractoriness. It is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy. The most common adverse reactions (1-2%) leading to discontinuation of intravenous amiodarone therapy are hypotension, asystole/cardiac arrest/pulseless electrical activity, VT, and cardiogenic shock. Other important adverse reactions are, torsade de pointes (TdP), congestive heart failure, and liver function test abnormalities. Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly. Since amiodarone is a substrate for CYP3A and CYP2C8, drugs/substances that inhibit these isoenzymes may decrease the metabolism and increase serum concentration of amiodarone.

CNS Activity

Curator's Comment:: The penetration of amiodarone into brain is poor.

Originator

Sources: DOI; 10.1007/978-1-4613-2827-8_26

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PACERONE

Approved Use

Amiodarone injection is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. Amiodarone also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with amiodarone, patients may be transferred to oral amiodarone therapy.

Launch Date

893894400000
Primary
PACERONE

Approved Use

Amiodarone injection is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. Amiodarone also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with amiodarone, patients may be transferred to oral amiodarone therapy [ see Dosage and Administration (2)

Launch Date

893894400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
23.8 ng/mL
2.5 mg/kg single, intravenous
dose: 2.5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DESETHYLAMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
13660 ng/mL
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2920 ng/mL
1.25 mg/kg single, intravenous
dose: 1.25 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7140 ng/mL
2.5 mg/kg single, intravenous
dose: 2.5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
41.2 ng/mL
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DESETHYLAMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
9 ng/mL
1.25 mg/kg single, intravenous
dose: 1.25 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DESETHYLAMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1.7 mg/L
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMIODARONE serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
16600 ng × h/mL
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3600 ng × h/mL
1.25 mg/kg single, intravenous
dose: 1.25 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
8100 ng × h/mL
2.5 mg/kg single, intravenous
dose: 2.5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
16900 ng × h/mL
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DESETHYLAMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14.6 day
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
14.2 day
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DESETHYLAMIODARONE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
4.62 h
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMIODARONE serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.023%
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMIODARONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 15 uM]
yes (co-administration study)
Comment: reversible inhibition; The area under the plasma concentration-time curve (AUC) of metoprolol increased from 767 before to 1,387 ug * hours/L after the amiodarone loading dose
yes [IC50 5.48 uM]
yes [IC50 >50 uM]
yes (co-administration study)
Comment: reversible inhibition; After treatment with 3 g amiodarone (phase I), this parameter (AUC of lidocaine) increased to 135.3 ± 34.6 (p = 0.016), whereas the AUC of MEGEX decreased from 19.2 ± 6.5 to 15.8 ± 8.3 μg/min/ml (p = 0.04).
yes [IC50 >50 uM]
yes (co-administration study)
Comment: reversible inhibition; The mean warfarin AUC during the amiodarone regimen increased to 200% of the control value of anticoagulant alone, from 624 ± 59 Rg/ml-hr to 1249 ± 115 p,g/ml-hr, a significant difference
yes [IC50 >50 uM]
yes (co-administration study)
Comment: reversible inhibition; The mean warfarin AUC during the amiodarone regimen increased to 200% of the control value of anticoagulant alone, from 624 ± 59 Rg/ml-hr to 1249 ± 115 p,g/ml-hr, a significant difference
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
likely (co-administration study)
Comment: CYP450 inhibitors: grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals, cimetidine, certain protease inhibitors: increased exposure of amiodarone. Avoid concomitant use. CYP450 inducers (St. John's Wort): reduced amiodarone serum levels
yes
likely (co-administration study)
Comment: CYP450 inhibitors: grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals, cimetidine, certain protease inhibitors: increased exposure of amiodarone. Avoid concomitant use. CYP450 inducers (St. John's Wort): reduced amiodarone serum levels
yes
likely (co-administration study)
Comment: CYP450 inhibitors: grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals, cimetidine, certain protease inhibitors: increased exposure of amiodarone. Avoid concomitant use. CYP450 inducers (St. John's Wort): reduced amiodarone serum levels
yes
likely (co-administration study)
Comment: CYP450 inhibitors: grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals, cimetidine, certain protease inhibitors: increased exposure of amiodarone. Avoid concomitant use. CYP450 inducers (St. John's Wort): reduced amiodarone serum levels
Page: 9
yes
likely (co-administration study)
Comment: CYP450 inhibitors: grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals, cimetidine, certain protease inhibitors: increased exposure of amiodarone. Avoid concomitant use. CYP450 inducers (St. John's Wort): reduced amiodarone serum levels
yes
likely (co-administration study)
Comment: CYP450 inhibitors: grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals, cimetidine, certain protease inhibitors: increased exposure of amiodarone. Avoid concomitant use. CYP450 inducers (St. John's Wort): reduced amiodarone serum levels
Page: 9
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Thyroid hormone alpha1 and beta1 receptor mRNA are downregulated by amiodarone in mouse myocardium.
1999 Aug
Acute fatal vasoplegia and asystole induced by intravenous amiodarone after cardiopulmonary bypass in a patient with preoperative cardiogenic shock.
1999 Dec
[Severe flecainide acetate poisoning. Apropos of a case].
1999 Feb
[Amiodarone induced retrobulbar neuritis. Clinical case].
1999 Jul
[Amiodarone-induced bilateral optic atrophy--a case report].
1999 Jun
[Treatment of cardiac insufficiency: does treatment depend on whether its cause is ischemic or idiopathic?].
1999 Jun
Interaction of amiodarone and triiodothyronine on the expression of beta-adrenoceptors in brown adipose tissue of rat.
1999 Mar
Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels.
1999 Mar
[The use of oral amiodarone as a chronic treatment in a patient with prior fulminant hepatitis due to intravenous amiodarone].
1999 Mar
Antiadrenergic effect of chronic amiodarone therapy in human heart failure.
1999 May
Features of amiodarone-induced optic neuropathy.
1999 May
Amiodarone interaction with beta-blockers: analysis of the merged EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) databases. The EMIAT and CAMIAT Investigators.
1999 May 4
Effects of chronic treatment by amiodarone on transmural heterogeneity of canine ventricular repolarization in vivo: interactions with acute sotalol.
1999 Nov
Meglumine antimoniate, amiodarone and torsades de pointes: a case report.
1999 Sep
Catheter ablation of atrial flutter due to amiodarone therapy for paroxysmal atrial fibrillation.
2000 Apr
Amiodarone-induced AV block and ventricular standstill. A forme fruste of an idiopathic long QT syndrome.
2000 Aug
Acute interstitial nephritis and fatal Stevens-Johnson syndrome after propylthiouracil therapy.
2000 Aug
Amiodarone-induced angioedema.
2000 Dec
Ocular toxicity of systemic medications: a case series.
2000 Jan
Amiodarone: clinical trials.
2000 Jan
Oral amiodarone increases the efficacy of direct-current cardioversion in restoration of sinus rhythm in patients with chronic atrial fibrillation.
2000 Jan
Amiodarone pulmonary, neuromuscular and ophthalmological toxicity.
2000 Mar-Apr
[Amiodarone-associated optic neuropathy: an independent syndrome? Three patients with bilateral optic neuropathy].
2000 Sep
Amiodarone optic neuropathy without disc edema.
2000 Sep
Amiodarone-related optic neuropathy.
2000 Sep-Oct
The effects of amiodarone on the thyroid.
2001 Apr
[Radiofrequency catheter ablation in children with Wolff-Parkinson-White syndrome and sudden cardiac death who had been resuscitated].
2001 Apr
Structure-activity relationships and electrophysiological effects of short-acting amiodarone homologs in guinea pig isolated heart.
2001 Apr
Intravenous amiodarone in cardiac arrest.
2001 Feb
Effects of amiodarone administration during pregnancy on neonatal thyroid function and subsequent neurodevelopment.
2001 Feb
Differential effects of dofetilide, amiodarone, and class lc drugs on left and right atrial refractoriness and left atrial vulnerability in pigs.
2001 Feb
Pharmacologic management of atrial fibrillation: current therapeutic strategies.
2001 Feb
Metabolism of amiodarone (part I): identification of a new hydroxylated metabolite of amiodarone.
2001 Feb
[The best in 2000 on arrhythmia].
2001 Jan
[Incidence and timing of thyroid dysfunction with long-term amiodarone therapy].
2001 Jan
Development of heart failure in bradycardic sick sinus syndrome.
2001 Jan
Thyroidectomy for selected patients with thyrotoxicosis.
2001 Jan
The frequency analysis of signal-averaged ECG of P wave as predictor of efficacy of class III antiarrhythmic drugs to maintain sinus rhythm in recurrent idiopathic atrial fibrillation.
2001 Jan
Amiodarone is safe and highly effective therapy for supraventricular tachycardia in infants.
2001 Jan
Chemical cardioversion of atrial fibrillation or flutter with ibutilide in patients receiving amiodarone therapy.
2001 Jan 16
"Stable" ventricular tachycardia is not a benign rhythm : insights from the antiarrhythmics versus implantable defibrillators (AVID) registry.
2001 Jan 16
Amiodarone-induced hyperthyroidism.
2001 Jan 22
Risk of torsades de pointes with non-cardiac drugs. Prolongation of QT interval is probably a class effect of fluoroquinolones.
2001 Jan 6
Does prophylaxis against atrial fibrillation after cardiac surgery reduce length of stay or hospital costs?
2001 Mar
The role of pharmacologic treatment to prevent sudden death in the implantable cardioverter defibrillator era.
2001 Mar
Moxifloxacin: clinical efficacy and safety.
2001 Mar 1
[Hyperthyroidism and heart].
2001 Mar 15
Prenatal diagnosis of junctional ectopic tachycardia.
2001 Mar-Apr
Patents

Sample Use Guides

Intravenous: Initial dose: 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:
Route of Administration: Other
In Vitro Use Guide
At concentrations ranging from 75-200 uM, amiodarone induced a significant and dose-dependent release of 51Cr in FRTL-5 cells. In the same molar concentrations, amiodarone was also cytotoxic in CHO cells. In hTF, the release of 51Cr produced by amiodarone occurred at a lower concentration (37.5 vs. 75 uM) and was significantly greater than that in FRTL-5 cells.
Name Type Language
AMIODARONE
INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
AMIODARONE [MI]
Common Name English
AMIODARONE [VANDF]
Common Name English
AMIODARONE [USAN]
Common Name English
AMIODARONE [MART.]
Common Name English
2-BUTYL-3-BENZOFURANYL 4-(2-(DIETHYLAMINO)ETHOXY)-3,5-DIIODOPHENYL KETONE
Systematic Name English
AMIODARONE [INN]
Common Name English
AMIODARONE [WHO-DD]
Common Name English
METHANONE, (2-BUTYL-3-BENZOFURANYL)(4-(2-(DIETHYLAMINO)ETHOXY)-3,5-DIIODOPHENYL)-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C47793
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
UCSF-FDA TRANSPORTAL AMIODARONE
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
WHO-VATC QC01BD01
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
FDA ORPHAN DRUG 70292
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
NDF-RT N0000175426
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 12.2
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
NCI_THESAURUS C93038
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
LIVERTOX 43
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
WHO-ATC C01BD01
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
Code System Code Type Description
EPA CompTox
1951-25-3
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
IUPHAR
2566
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
NDF-RT
N0000182141
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
MESH
D000638
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
DRUG BANK
DB01118
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
FDA UNII
N3RQ532IUT
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
RXCUI
703
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY RxNorm
ECHA (EC/EINECS)
217-772-1
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
WIKIPEDIA
AMIODARONE
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
DRUG CENTRAL
176
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
NDF-RT
N0000182138
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY Cytochrome P450 1A2 Inhibitors [MoA]
CAS
1951-25-3
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
EVMPD
SUB05451MIG
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
PUBCHEM
2157
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
NCI_THESAURUS
C62002
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
NDF-RT
N0000185503
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY P-Glycoprotein Inhibitors [MoA]
ChEMBL
CHEMBL633
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
NDF-RT
N0000185504
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY Cytochrome P450 2C9 Inhibitors [MoA]
MERCK INDEX
M1748
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY Merck Index
NDF-RT
N0000182137
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY Cytochrome P450 2D6 Inhibitors [MoA]
LACTMED
Amiodarone
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY
INN
2012
Created by admin on Sat Jun 26 10:43:36 UTC 2021 , Edited by admin on Sat Jun 26 10:43:36 UTC 2021
PRIMARY