Dronedarone

Details

Stereochemistry	ACHIRAL
Molecular Formula	C31H44N2O5S
Molecular Weight	556.756
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCN(CCCC)CCCOC1=CC=C(C=C1)C(=O)C2=C(CCCC)OC3=C2C=C(NS(C)(=O)=O)C=C3

InChI

InChIKey=ZQTNQVWKHCQYLQ-UHFFFAOYSA-N

InChI=1S/C31H44N2O5S/c1-5-8-12-29-30(27-23-25(32-39(4,35)36)15-18-28(27)38-29)31(34)24-13-16-26(17-14-24)37-22-11-21-33(19-9-6-2)20-10-7-3/h13-18,23,32H,5-12,19-22H2,1-4H3

HIDE SMILES / InChI

Molecular Formula	C31H44N2O5S
Molecular Weight	556.756
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/ppa/dronedarone.html | https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7fa41601-7fb5-4155-8e50-2ae903f0d2d6 | http://www.rxlist.com/multaq-drug.htm

Dronedarone is an antiarrhythmic that is FDA approved for the treatment of atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation (AF). Dronedarone is multichannel blocker. Common adverse reactions include abdominal pain, diarrhea, indigestion, nausea, vomiting, asthenia and raised serum creatinine. Dronedarone has potentially important pharmacodynamics interactions: Digoxin: Consider discontinuation or halve dose of digoxin before treatment and monitor; Calcium channel blockers (CCB): Initiate CCB with low dose and increase after ECG verification of tolerability; Beta-blockers: May provoke excessive bradycardia, Initiate with low dose and increase after ECG verification of tolerability.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Inward rectifier potassium channel 2 5 Target ID: CHEMBL1914276 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25182566	Blocker 555
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 14 Target ID: CHEMBL1250417 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21279331	Blocker 555	1.0 µM [IC50]
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17389667 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
Atrial fibrillation 131 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf	Primary		Approved 8583	MULTAQ Approved Use MULTAQ® is indicated to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation (AF) [see Clinical Studies (14) Launch Date 2009
Atrial flutter 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf	Primary		Approved 8583	MULTAQ Approved Use MULTAQ® is indicated to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation (AF) [see Clinical Studies (14) Launch Date 2009

C_max

Value	Dose	Co-administered	Analyte	Population
96.2 ng/mL EXPERIMENT https://onlinelibrary.wiley.com/doi/full/10.1046/j.1472-8206.2003.00216.x	1600 mg single, oral dose: 1600 mg route of administration: Oral experiment type: SINGLE co-administered: METOPROLOL	METOPROLOL	DRONEDARONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1386 ng × h/mL EXPERIMENT https://onlinelibrary.wiley.com/doi/full/10.1046/j.1472-8206.2003.00216.x	1600 mg single, oral dose: 1600 mg route of administration: Oral experiment type: SINGLE co-administered: METOPROLOL	METOPROLOL	DRONEDARONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
12 h EXPERIMENT https://onlinelibrary.wiley.com/doi/full/10.1046/j.1472-8206.2003.00216.x	1600 mg single, oral dose: 1600 mg route of administration: Oral experiment type: SINGLE co-administered: METOPROLOL	METOPROLOL	DRONEDARONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 2 times / day steady, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf	unhealthy, 20-97 years Health Status: unhealthy Age Group: 20-97 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf	Disc. AE: Gastrointestinal disorders, QT interval prolonged... AEs leading to discontinuation/dose reduction: Gastrointestinal disorders (3.2%) QT interval prolonged (1.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf
1600 mg 2 times / day multiple, oral Highest studied dose Dose: 1600 mg, 2 times / day Route: oral Route: multiple Dose: 1600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17056831	healthy, 21-40 years Health Status: healthy Age Group: 21-40 years Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17056831	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17056831
400 mg 2 times / day steady, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_MedR_P2.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_MedR_P2.pdf	Disc. AE: Diarrhea, Nausea... AEs leading to discontinuation/dose reduction: Diarrhea (6.7%) Nausea (3.9%) Abdominal pain upper (2%) Abdominal pain (1.9%) Vomiting (1.7%) Dyspepsia (1.3%) Nasopharyngitis (3.7%) Upper respiratory tract infection (2.9%) Dizziness (3.4%) Blood creatinine increased (2.5%) Hepatic enzyme increased (1.2%) Blood urea increased (0.4%) Bradycardia (2.6%) Palpitations (1.1%) Cardiac failure congestive (1.3%) Cardiac failure (0.8%) Fatigue (2.7%) Oedema peripheral (4.2%) Back pain (3.3%) Arthralgia (3.1%) Pain in extremity (2.1%) Cough (2.2%) Dyspnoea (2.3%) Vertigo (1.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_MedR_P2.pdf
400 mg 2 times / day steady, oral Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf	Other AEs: Heart failure... Other AEs: Heart failure (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf
600 mg 2 times / day multiple, oral Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_MedR_P2.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_MedR_P2.pdf	Disc. AE: Diarrhea, Vomiting... AEs leading to discontinuation/dose reduction: Diarrhea (7.6%) Vomiting (1.5%) Dyspepsia (3%) Abdominal pain (1.5%) Nasopharyngitis (4.5%) Electrocardiogram QT prolonged (1.5%) Blood creatinine increased (1.5%) Hepatic enzyme increased (4.5%) Blood urea increased (3%) Bradycardia (1.5%) Palpitations (6.1%) Cardiac failure congestive (4.5%) Cardiac failure (4.5%) Fatigue (4.5%) Cough (1.5%) Hypokalemia (3%) Vertigo (4.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_MedR_P2.pdf
800 mg 2 times / day multiple, oral Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_MedR_P2.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_MedR_P2.pdf	Disc. AE: Diarrhea, Nausea... AEs leading to discontinuation/dose reduction: Diarrhea (29%) Nausea (8.1%) Vomiting (3.2%) Abdominal pain (3.2%) Influenza (3.2%) Upper respiratory tract infection (1.6%) Dizziness (4.8%) Electrocardiogram QT prolonged (3.2%) Hepatic enzyme increased (1.6%) Blood urea increased (3.2%) Bradycardia (6.5%) Palpitations (4.8%) Cardiac failure congestive (1.6%) Cardiac failure (1.6%) Fatigue (3.2%) Atrial tachycardia (4.8%) Cough (4.8%) Vertigo (3.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_MedR_P2.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inducer 440 inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057 CYP2E1 1060 P-gp 1741 OAT1 725 OAT3 747 OCT1 620 OATP1B1 1079 OATP1B3 961	CYP3A 220 CYP1A2 1197 P-gp 2052	CYP1A2 832 CYP2A6 86 CYP3A 142 CYP2C8 198 CYP2C19 329

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022425s029lbl.pdf#page=13 Page: 13.0	likely
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022425s029lbl.pdf#page=13 Page: 13.0	likely
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76,89,194	moderate [Ki 8.12 uM]	yes (co-administration study) Comment: dronedarone increased verapamil exposure by 1.4- fold, and nisoldipine exposure by 1.5- fold; dronedarone increased simvastatin, a sensitive CYP3A substrate, and simvastatin acid exposure by 4- fold and 2- fold, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76,89,194
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	no
CYP2A6 911	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	no
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	no
CYP3A 317	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	not significant
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	not significant
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	not significant
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022425s029lbl.pdf#page=13 Page: 13.0	not significant
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022425s029lbl.pdf#page=13 Page: 13.0	not significant
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022425s029lbl.pdf#page=13 Page: 13.0	not significant
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	not significant	weak (co-administration study) Comment: dronedarone increased S-warfarin exposure by 1.2- fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76,90	strong [IC50 0.97 uM]	yes (co-administration study) Comment: IC50 value obtained using vincristine as substrate; increased S-warfarin exposure by 1.2- fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76,90
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76,89,194	weak [Ki 4.37 uM]	yes (co-administration study) Comment: dronedarone increased metoprolol exposure by 1.6- and 2.3- fold, respectively; increased propranolol exposure by 1.3- fold; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76,89,194

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A 220	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76,89	major	yes (co-administration study) Comment: administration of ketoconazole resulted in a 17- to 25- fold increase in dronedarone exposure; administration with rifampicin decreased dronedarone exposure by 80% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76,89
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_ClinPharm_P1.pdf#page=76 Page: 76.0	unlikely

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022425s000_Pharm_P1.pdf#page=59 Page: 59.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:50659	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50659
ChemicalBook	CB11117179	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB11117179
eMolecules	30152747	https://www.emolecules.com/cgi-bin/more?vid=30152747
MolPort	MolPort-006-170-000	https://www.molport.com/shop/molecule-link/MolPort-006-170-000
ZINC	ZINC000049933061	http://zinc15.docking.org/substances/ZINC000049933061

PubMed

Title	Date	PubMed
Newer antiarrhythmic drugs.	2001 May-Jun	11516042
Chronic and acute effects of dronedarone on the action potential of rabbit atrial muscle preparations: comparison with amiodarone.	2002 May	11973411
Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes.	2003 Aug	12890054
Electrophysiologic characterization of dronedarone in guinea pig ventricular cells.	2003 Feb	12548079
Trials of new antiarrhythmic drugs for maintenance of sinus rhythm in patients with atrial fibrillation.	2004	14739742
Oral class III antiarrhythmics: what is new?	2004 Jan	14688634
The novel antiarrhythmic drug dronedarone: comparison with amiodarone.	2005 Fall	16252015
Pharmacological treatment of atrial fibrillation: mechanisms of action and efficacy of class III drugs.	2006	16787210
[Dronedarone--a new therapeutic option for controlling atrial rhythm and ventricular frequency].	2006 Aug 25	16921447
Do we need pharmacological therapy for atrial fibrillation in the ablation era?	2006 Dec	17340189
Dronedarone: a new antiarrhythmic agent.	2006 Feb	16541184
Dose-dependent effects of oral dronedarone on the circadian variation of RR and QT intervals in healthy subjects: implications for antiarrhythmic actions.	2006 Sep	17056831
Drug evaluation: dronedarone, a novel non-iodinated anti-arrhythmic agent.	2006 Sep	17002263
Topics on the Na+/Ca2+ exchanger: pharmacological characterization of Na+/Ca2+ exchanger inhibitors.	2006 Sep	16990699
Dronedarone: an emerging agent with rhythm- and rate-controlling effects.	2006 Sep	16939434
Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter.	2007 Apr	17389667
Maintaining sinus rhythm--making treatment better than the disease.	2007 Sep 6	17804851
Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter.	2007 Sep 6	17804843
[Efficacy of dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. Results of the EURIDIS and ADONIS].	2008	18789030
Relationship among amiodarone, new class III antiarrhythmics, miscellaneous agents and acquired long QT syndrome.	2008	18651412
[Amiodaron for treatment of perioperative cardiac arrythmia: a broad spectrum antiarrythmetic agent?].	2008 Dec	18704341
Pharmacotherapy for atrial arrhythmias: present and future.	2008 Jun	18456197
Acute inhibitory effect of dronedarone, a noniodinated benzofuran analogue of amiodarone, on Na+/Ca2+ exchange current in guinea pig cardiac ventricular myocytes.	2008 Jun	18392809
Dronedarone: a new treatment for atrial fibrillation.	2008 Nov	18702618
Dronedarone for the control of ventricular rate in permanent atrial fibrillation: the Efficacy and safety of dRonedArone for the cOntrol of ventricular rate during atrial fibrillation (ERATO) study.	2008 Sep	18760136
New horizons in antiarrhythmic therapy: will novel agents overcome current deficits?	2008 Sep 22	18790110
Trial watch: novel antiarrhythmic agent shows promise in Phase III trial.	2009 Apr	19337265
Alternatives to amiodarone: search for the Holy Grail.	2009 Apr	19223364
Dronedarone for atrial fibrillation--an odyssey.	2009 Apr 30	19403901
Effect of dronedarone on cardiovascular events in atrial fibrillation.	2009 Feb 12	19213680
Benzofuran derivatives and the thyroid.	2009 Jan	18727707
Major recent trials in cardiovascular diseases.	2009 Mar	19332959
New pharmacological options for patients with atrial fibrillation: the ATHENA trial.	2009 May	19406061

Patents

Sample Use Guides

In Vivo Use Guide

One tablet of 400 mg twice a day with morning and evening meals.

Route of Administration: Oral

In Vitro Use Guide

In isolated ventricular myocytes, dronedarone inhibited rapidly activating delayed-rectifier K+ current (I(Kr)) (median inhibitory concentration [IC50] /= 30 uM).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:24:49 GMT 2025` Edited by `admin` on `Mon Mar 31 18:24:49 GMT 2025`
Record UNII	JQZ1L091Y2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SR-33589

Preferred Name

English

Dronedarone

Official Name

English

Dronedarone [INN]

Common Name

English

Methanesulfonamide, N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]-

Systematic Name

English

SR33589

Code

English

Dronedarone [VANDF]

Common Name

English

N-[2-Butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]benzofuran-5-yl]methanesulfonamide

Systematic Name

English

Dronedarone [EMA EPAR]

Common Name

English

Dronedarone [WHO-DD]

Common Name

English

N-[2-Butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide

Systematic Name

English

Dronedarone [MI]

Common Name

English

Dronedarone [MART.]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC01BD07