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Details

Stereochemistry ACHIRAL
Molecular Formula C25H29I2NO3.ClH
Molecular Weight 681.773
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMIODARONE HYDROCHLORIDE

SMILES

Cl.CCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C3=C(O1)C=CC=C3

InChI

InChIKey=ITPDYQOUSLNIHG-UHFFFAOYSA-N
InChI=1S/C25H29I2NO3.ClH/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;1H

HIDE SMILES / InChI

Molecular Formula C25H29I2NO3
Molecular Weight 645.3116
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including: 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

1998
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

1998
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: 9.0
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: 9.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Ocular toxicology.
1994 Dec
Amiodarone-induced depression.
1999 Apr
Acetazolamide-responsive periodic ataxia induced by amiodarone.
1999 Mar
[Medication-induced vocal cord paralysis as an uncommon cause of cord paralysis].
1999 Sep
[Congenital left ventricular aneurysms and diverticula: clinical findings, diagnosis and course].
1999 Sep 4
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
Amiodarone pulmonary, neuromuscular and ophthalmological toxicity.
2000 Mar-Apr
[Amiodarone-associated optic neuropathy: an independent syndrome? Three patients with bilateral optic neuropathy].
2000 Sep
Protection against drug- and chemical-induced multiorgan toxicity by a novel IH636 grape seed proanthocyanidin extract.
2001
Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture.
2001 Feb
Oral anticoagulants. Pharmacologic issues for use in the elderly.
2001 Feb
Pharmacologic management of atrial fibrillation: current therapeutic strategies.
2001 Feb
Bioavailability of amiodarone tablets administered with and without food in healthy subjects.
2001 Feb 15
[How I treat...persistent atrial fibrillation, by internal cardioversion, in a patient with exreme obesity].
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
Amiodarone is safe and highly effective therapy for supraventricular tachycardia in infants.
2001 Jan
"Stable" ventricular tachycardia is not a benign rhythm : insights from the antiarrhythmics versus implantable defibrillators (AVID) registry.
2001 Jan 16
Risk of torsades de pointes with non-cardiac drugs. Prolongation of QT interval is probably a class effect of fluoroquinolones.
2001 Jan 6
Efficacy of sequential antiarrhythmic treatment in sinus rhythm maintenance after successful electrocardioversion in patients with chronic non-valvular atrial fibrillation.
2001 Jan-Feb
Torsade de pointes induced by intravenous and long-term oral amiodarone therapy in a patient with dilated cardiomyopathy.
2001 Mar
Moxifloxacin: clinical efficacy and safety.
2001 Mar 1
[Hyperthyroidism and heart].
2001 Mar 15
Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial.
2001 Mar 17
Patents

Sample Use Guides

Intravenous: Initial dose: 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen: -Loading infusions: 150 mg over the first 10 minutes (15 mg/min), followed by 360 mg over the next 6 hours (1 mg/min) -Maintenance infusion: 540 mg over the remaining 18 hours (0.5 mg/min) Maintenance dose: After the first 24 hours, continue the maintenance infusion rate of 0.5 mg/min; may increase infusion rate to achieve effective arrhythmia suppression. -Supplemental infusions: 150 mg over 10 minutes (15 mg/min) for breakthrough episodes of ventricular fibrillation (VF) or hemodynamically unstable ventricular tachycardia(VT) Maximum dose: Initial infusion rate: 30 mg/min Oral: Loading dose: 800 to 1600 mg orally per day for 1 to 3 weeks (occasionally longer) until adequate arrhythmia control is achieved or if side effects become prominent, then switch to adjustment dose Adjustment dose: 600 to 800 mg orally per day for 1 month, then switch to maintenance dose Maintenance dose: 400 mg orally per day
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:02:41 GMT 2023
Edited
by admin
on Fri Dec 15 15:02:41 GMT 2023
Record UNII
976728SY6Z
Record Status Validated (UNII)
Record Version
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Name Type Language
AMIODARONE HYDROCHLORIDE
EP   HSDB   JAN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
Common Name English
AMIODARONE HYDROCHLORIDE [HSDB]
Common Name English
Methanone, (2-butyl-3-benzofuranyl)[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]-, hydrochloride (1:1)
Systematic Name English
AMIODARONE HYDROCHLORIDE [MART.]
Common Name English
AMIODARONE HYDROCHLORIDE [JAN]
Common Name English
Ketone, 2-butyl-3-benzofuranyl 4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl, hydrochloride
Common Name English
AMIODARONE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
Amiodarone hydrochloride [WHO-DD]
Common Name English
AMIODARONE HYDROCHLORIDE [VANDF]
Common Name English
AMIODARONE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
MIODARON
Common Name English
NSC-85442
Code English
ORTACRONE
Common Name English
AMIODARONE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
SKF 33134-A
Code English
AMIODAR
Common Name English
SKF-33134-A
Code English
RITMOCARDYL
Common Name English
2-Butyl-3-benzofuranyl 4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl ketone hydrochloride
Systematic Name English
AMIODARONE HCL
Common Name English
CORDARONE
Brand Name English
AMIODARONE HYDROCHLORIDE [MI]
Common Name English
AMIODARONE HYDROCHLORIDE [USP-RS]
Common Name English
PACERONE
Brand Name English
L-3428
Code English
METHANONE, (2-BUTYL-3-BENZOFURANYL)(4-(2-(DIETHYLAMINO)ETHOXY)-3,5-DIIODOPHENYL)- HYDROCHLORIDE
Systematic Name English
NEXTERONE
Brand Name English
TRANGOREX
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C93038
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
FDA ORPHAN DRUG 77293
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
NCI_THESAURUS C47793
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
Code System Code Type Description
RS_ITEM_NUM
1027302
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
PRIMARY
ECHA (EC/EINECS)
243-293-2
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
PRIMARY
NSC
85442
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
PRIMARY
ChEMBL
CHEMBL633
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
PRIMARY
EPA CompTox
DTXSID7037185
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
PRIMARY
DAILYMED
976728SY6Z
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
PRIMARY
RXCUI
203114
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
PRIMARY RxNorm
PUBCHEM
29770
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PRIMARY
HSDB
6525
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PRIMARY
SMS_ID
100000092847
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
PRIMARY
NCI_THESAURUS
C236
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PRIMARY
EVMPD
SUB00472MIG
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PRIMARY
FDA UNII
976728SY6Z
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PRIMARY
DRUG BANK
DBSALT000355
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PRIMARY
CAS
19774-82-4
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
PRIMARY
MERCK INDEX
m1748
Created by admin on Fri Dec 15 15:02:41 GMT 2023 , Edited by admin on Fri Dec 15 15:02:41 GMT 2023
PRIMARY Merck Index
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
PARENT -> SALT/SOLVATE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
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CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (TLC)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
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ACTIVE MOIETY