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dronedarone 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
antiarrhythmics	4112	141626-36-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: dronedarone multaq dronedarone hydrochloride SR33598B dronedarone HCl	Dronedarone has antiarrhythmic properties belonging to all four Vaughan-Williams classes, but the contribution of each of these activities to the clinical effect is unknown. Molecular weight: 556.76 Formula: C31H44N2O5S CLOGP: 8.57 LIPINSKI: 2 HAC: 7 HDO: 1 TPSA: 88.85 ALOGS: -5.44 ROTB: 17 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

dronedarone
multaq
dronedarone hydrochloride
SR33598B
dronedarone HCl

Dronedarone has antiarrhythmic properties belonging to all four Vaughan-Williams classes, but the contribution of each of these activities to the clinical effect is unknown.

Molecular weight: 556.76
Formula: C31H44N2O5S
CLOGP: 8.57
LIPINSKI: 2
HAC: 7
HDO: 1
TPSA: 88.85
ALOGS: -5.44
ROTB: 17

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.80	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.50 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	0 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	20.53 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	20 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	33.33 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.02 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	16 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
July 1, 2009	FDA	SANOFI AVENTIS US

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Atrial fibrillation	189.64	21.66	127	6185	116509	63366201
Blood creatinine increased	180.77	21.66	111	6201	87733	63394977
Drug interaction	172.25	21.66	158	6154	228973	63253737
International normalised ratio increased	125.29	21.66	70	6242	46355	63436355
Dyspnoea	109.71	21.66	217	6095	661096	62821614
Torsade de pointes	101.10	21.66	41	6271	13310	63469400
Cardiac failure	94.39	21.66	75	6237	89067	63393643
Cardiac failure congestive	79.58	21.66	69	6243	92364	63390346
Gastrointestinal haemorrhage	74.77	21.66	63	6249	81113	63401597
Ventricular tachycardia	64.63	21.66	34	6278	19945	63462765
Hepatocellular injury	62.37	21.66	37	6275	27344	63455366
Glomerular filtration rate decreased	61.64	21.66	29	6283	13412	63469298
Subchondral insufficiency fracture	57.19	21.66	9	6303	49	63482661
Renal failure	56.69	21.66	64	6248	117588	63365122
Alanine aminotransferase increased	56.15	21.66	60	6252	103710	63379000
Palpitations	50.37	21.66	59	6253	112711	63369999
Aspartate aminotransferase increased	48.48	21.66	52	6260	90225	63392485
Arrhythmia	42.26	21.66	33	6279	38107	63444603
Atrial flutter	41.49	21.66	20	6292	9752	63472958
Gamma-glutamyltransferase increased	41.11	21.66	31	6281	34000	63448710
Bradycardia	37.24	21.66	41	6271	73186	63409524
Electrocardiogram R on T phenomenon	35.27	21.66	5	6307	11	63482699
Oedema peripheral	33.27	21.66	64	6248	189447	63293263
Blood bilirubin increased	28.48	21.66	26	6286	37114	63445596
Transaminases increased	28.13	21.66	24	6288	31343	63451367
Liver function test abnormal	28.06	21.66	29	6283	48152	63434558
Acute kidney injury	27.17	21.66	72	6240	263343	63219367
Blood alkaline phosphatase increased	27.10	21.66	27	6285	42940	63439770
Hyperthyroidism	26.22	21.66	17	6295	14656	63468054
Atrioventricular block first degree	25.30	21.66	13	6299	7260	63475450
Pain	24.08	21.66	23	6289	740605	62742105
Brain natriuretic peptide increased	23.13	21.66	11	6301	5202	63477508
Product residue present	22.70	21.66	10	6302	3969	63478741
Rectal haemorrhage	22.44	21.66	26	6286	49004	63433706
Sinus arrest	21.96	21.66	8	6304	1941	63480769
Ventricular fibrillation	21.83	21.66	14	6298	11853	63470857
Gastroenteritis clostridial	21.81	21.66	6	6306	586	63482124

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Blood creatinine increased	141.49	21.41	120	5616	94856	34856339
Atrial fibrillation	126.46	21.41	126	5610	122267	34828928
Drug interaction	110.89	21.41	159	5577	225787	34725408
Dyspnoea	101.94	21.41	203	5533	376579	34574616
Ventricular tachycardia	86.45	21.41	54	5682	26525	34924670
International normalised ratio increased	85.46	21.41	67	5669	47260	34903935
Cardiac failure	66.06	21.41	78	5658	91170	34860025
Gastrointestinal haemorrhage	61.35	21.41	74	5662	88403	34862792
Glomerular filtration rate decreased	48.96	21.41	29	5707	12932	34938263
Bradycardia	45.72	21.41	59	5677	75359	34875836
Cardiac failure congestive	45.64	21.41	62	5674	83208	34867987
Ventricular fibrillation	44.65	21.41	34	5702	22920	34928275
Cholangitis sclerosing	43.58	21.41	14	5722	1407	34949788
Atrial flutter	41.64	21.41	28	5708	15546	34935649
Electrocardiogram QT prolonged	39.97	21.41	41	5695	40911	34910284
Hyperthyroidism	38.23	21.41	23	5713	10543	34940652
Xanthopsia	38.04	21.41	8	5728	147	34951048
Arrhythmia	37.04	21.41	37	5699	35771	34915424
Torsade de pointes	32.21	21.41	18	5718	7191	34944004
Creatinine renal clearance decreased	31.77	21.41	14	5722	3367	34947828
Cardiac ablation	26.47	21.41	9	5727	1079	34950116
Blood loss anaemia	24.99	21.41	16	5720	8178	34943017
Liver function test abnormal	24.83	21.41	28	5708	31046	34920149
Sinoatrial block	24.01	21.41	7	5729	508	34950687
Pulmonary toxicity	23.85	21.41	14	5722	6133	34945062
Alanine aminotransferase increased	23.33	21.41	45	5691	80770	34870425
Gamma-glutamyltransferase increased	22.78	21.41	26	5710	29205	34921990
Hepatic enzyme increased	22.75	21.41	30	5706	39050	34912145
Palpitations	22.21	21.41	30	5706	39956	34911239
Underdose	21.62	21.41	18	5718	13762	34937433

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Blood creatinine increased	262.54	20.09	191	10029	154866	79579302
Drug interaction	254.29	20.09	288	9932	414895	79319273
Atrial fibrillation	205.24	20.09	183	10037	197703	79536465
Dyspnoea	167.16	20.09	349	9871	856676	78877492
International normalised ratio increased	158.39	20.09	111	10109	84610	79649558
Gastrointestinal haemorrhage	119.18	20.09	119	10101	147600	79586568
Cardiac failure congestive	97.35	20.09	105	10115	142297	79591871
Torsade de pointes	96.89	20.09	48	10172	19264	79714904
Ventricular tachycardia	90.28	20.09	60	10160	41875	79692293
Cardiac failure	88.47	20.09	104	10116	154738	79579430
Glomerular filtration rate decreased	83.99	20.09	46	10174	22656	79711512
Hepatocellular injury	74.38	20.09	56	10164	47537	79686631
Ventricular fibrillation	69.48	20.09	46	10174	31880	79702288
Alanine aminotransferase increased	68.73	20.09	94	10126	162476	79571692
Bradycardia	65.97	20.09	84	10136	135473	79598695
Aspartate aminotransferase increased	59.85	20.09	81	10139	138560	79595608
Gamma-glutamyltransferase increased	59.33	20.09	52	10168	54628	79679540
Palpitations	59.31	20.09	77	10143	126533	79607635
Atrial flutter	56.58	20.09	35	10185	21590	79712578
Subchondral insufficiency fracture	53.08	20.09	9	10211	62	79734106
Renal failure	47.31	20.09	89	10131	200879	79533289
Arrhythmia	46.83	20.09	48	10172	61224	79672944
Hyperthyroidism	45.91	20.09	31	10189	22178	79711990
Electrocardiogram QT prolonged	42.35	20.09	55	10165	90331	79643837
Cholangitis sclerosing	38.48	20.09	14	10206	2623	79731545
Blood loss anaemia	35.34	20.09	23	10197	15475	79718693
Blood bilirubin increased	35.32	20.09	43	10177	66189	79667979
Oedema peripheral	34.63	20.09	90	10130	252198	79481970
Xanthopsia	33.41	20.09	8	10212	347	79733821
Blood alkaline phosphatase increased	33.40	20.09	41	10179	63623	79670545
Cardiac ablation	33.02	20.09	12	10208	2241	79731927
Transaminases increased	31.58	20.09	36	10184	51707	79682461
Underdose	30.98	20.09	29	10191	33122	79701046
Extrasystoles	30.13	20.09	16	10204	7403	79726765
Brain natriuretic peptide increased	30.08	20.09	17	10203	8883	79725285
Sinus bradycardia	29.38	20.09	25	10195	25222	79708946
Liver function test abnormal	28.29	20.09	38	10182	64437	79669731
Dizziness	27.04	20.09	136	10084	526305	79207863
Cholestatic liver injury	26.93	20.09	13	10207	4928	79729240
Electrocardiogram R on T phenomenon	26.84	20.09	4	10216	10	79734158
Neutropenia	26.40	20.09	3	10217	287707	79446461
Ventricular extrasystoles	26.02	20.09	21	10199	19683	79714485
Blood urea increased	24.91	20.09	31	10189	48759	79685409
Atrioventricular block second degree	24.80	20.09	14	10206	7298	79726870
Acute kidney injury	24.46	20.09	131	10089	519273	79214895
Jaundice	22.73	20.09	31	10189	53318	79680850
Atrioventricular block first degree	22.44	20.09	16	10204	12475	79721693
Pain	22.22	20.09	35	10185	703767	79030401
Haemorrhage	22.21	20.09	41	10179	91077	79643091
Pulmonary toxicity	21.97	20.09	16	10204	12898	79721270
Tachycardia	21.93	20.09	61	10159	177707	79556461
Sinus arrest	21.17	20.09	10	10210	3612	79730556
Atrioventricular block	20.77	20.09	16	10204	14025	79720143
Hepatitis toxic	20.62	20.09	11	10209	5136	79729032
Sudden cardiac death	20.46	20.09	11	10209	5214	79728954

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	C01BD07	CARDIOVASCULAR SYSTEM CARDIAC THERAPY ANTIARRHYTHMICS, CLASS I AND III Antiarrhythmics, class III
FDA EPC	N0000175426	Antiarrhythmic
MeSH PA	D000889	Anti-Arrhythmia Agents
MeSH PA	D002317	Cardiovascular Agents
CHEBI has role	CHEBI:35703	Xenobiotic
CHEBI has role	CHEBI:38070	antiarrhythmic agent
CHEBI has role	CHEBI:78298	environmental contaminants

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Atrial fibrillation	indication	49436004	DOID:0060224
Paroxysmal atrial fibrillation	indication	282825002
Complete atrioventricular block	contraindication	27885002
Torsades de pointes	contraindication	31722008
Sick sinus syndrome	contraindication	36083008	DOID:13884
Hypokalemia	contraindication	43339004
Chronic heart failure	contraindication	48447003
Bradycardia	contraindication	48867003
Hepatic failure	contraindication	59927004
Prolonged QT interval	contraindication	111975006
Liver function tests abnormal	contraindication	166603001
Hypomagnesemia	contraindication	190855004
Second degree atrioventricular block	contraindication	195042002
Decompensated cardiac failure	contraindication	195111005
Pregnancy, function	contraindication	289908002
Cardiovascular event risk	contraindication	395112001
Breastfeeding (mother)	contraindication	413712001
Congenital long QT syndrome	contraindication	442917000
Worsening of Chronic Heart Failure	contraindication

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	7.65	acidic
pKa2	9.7	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 400MG BASE	MULTAQ	SANOFI AVENTIS US	N022425	July 1, 2009	RX	TABLET	ORAL	8410167	April 16, 2029	REDUCTION IN RISK OF HOSPITALIZATION IN PATIENTS WITH A HISTORY OF PAROXYSMAL OR PERSISTENT AF WITHOUT SEVERE HEART FAILURE AND WITH ONE OR MORE RISK FACTORS BY ADMINISTRATION TWICE A DAY WITH MORNING AND EVENING MEALS
EQ 400MG BASE	MULTAQ	SANOFI AVENTIS US	N022425	July 1, 2009	RX	TABLET	ORAL	8410167	April 16, 2029	TREATMENT OF PATIENTS WITH A HISTORY OF PAROXYSMAL OR PERSISTENT AF WITHOUT SEVERE HEART FAILURE AND WITH ONE OR MORE RISK FACTORS BY ADMINISTRATION TWICE A DAY WITH MORNING AND EVENING MEALS
EQ 400MG BASE	MULTAQ	SANOFI AVENTIS US	N022425	July 1, 2009	RX	TABLET	ORAL	9107900	April 16, 2029	REDUCTION IN RISK OF HOSPITALIZATION IN PATIENTS WITH CORONARY HEART DISEASE AND A HISTORY OF PAROXYSMAL OR PERSISTENT AF AND WITH ONE OR MORE RISK FACTORS BY ADMINISTRATION TWICE A DAY WITH MORNING AND EVENING MEALS
EQ 400MG BASE	MULTAQ	SANOFI AVENTIS US	N022425	July 1, 2009	RX	TABLET	ORAL	9107900	April 16, 2029	REDUCTION IN RISK OF HOSPITALIZATION IN PATIENTS WITH STABLE NYHA CLASS III HEART FAILURE AND A HISTORY OF PAROXYSMAL OR PERSISTENT AF AND WITH ONE OR MORE RISK FACTORS BY ADMINISTRATION TWICE A DAY WITH MORNING AND EVENING MEALS
EQ 400MG BASE	MULTAQ	SANOFI AVENTIS US	N022425	July 1, 2009	RX	TABLET	ORAL	8602215	June 30, 2031	MANAGEMENT OF RISK OF DRONEDARONE/BETA-BLOCKER INTERACTION IN PATIENTS IN SINUS RHYTHM WITH A HISTORY OF PAROXYSMAL OR PERSISTENT AF

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1	Ion channel	O60741	HCN1_HUMAN	BLOCKER			SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2	Ion channel	Q9UL51	HCN2_HUMAN	BLOCKER			SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3	Ion channel	Q9P1Z3	HCN3_HUMAN	BLOCKER			SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4	Ion channel	Q9Y3Q4	HCN4_HUMAN	BLOCKER			SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Potassium voltage-gated channel subfamily A member 5	Ion channel	P22460	KCNA5_HUMAN		IC50	5.63	CHEMBL
Thyroid hormone receptor alpha	Nuclear hormone receptor	P10827	THA_HUMAN		IC50	4.23	WOMBAT-PK
THAP domain-containing protein 1	Unclassified	Q9NVV9	THAP1_HUMAN		IC50	4.23	WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	6.50	CHEMBL
Voltage-dependent calcium channel gamma-1 subunit	Ion channel	Q06432	CCG1_HUMAN		IC50	6.70	WOMBAT-PK
Potassium voltage-gated channel subfamily KQT member 2	Ion channel	O43526	KCNQ2_HUMAN	BLOCKER	IC50	8	WOMBAT-PK
NACHT, LRR and PYD domains-containing protein 3	Unclassified		NLRP3_MOUSE		IC50	5.17	CHEMBL

External reference:

ID	Source
4028918	VUID
N0000179804	NUI
D02537	KEGG_DRUG
141625-93-6	SECONDARY_CAS_RN
4028918	VANDF
C0766326	UMLSCUI
CHEBI:50659	CHEBI
CHEMBL184412	ChEMBL_ID
CHEMBL1201729	ChEMBL_ID
D000077764	MESH_DESCRIPTOR_UI
DB04855	DRUGBANK_ID
7465	IUPHAR_LIGAND_ID
7382	INN_ID
JQZ1L091Y2	UNII
208898	PUBCHEM_CID
233698	RXNORM
166180	MMSL
26593	MMSL
33190	MMSL
d07458	MMSL
013186	NDDF
013187	NDDF
443195003	SNOMEDCT_US
443310000	SNOMEDCT_US
703121007	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Multaq	HUMAN PRESCRIPTION DRUG LABEL	1	0024-4142	TABLET, FILM COATED	400 mg	ORAL	NDA	29 sections
Multaq	HUMAN PRESCRIPTION DRUG LABEL	1	54868-3086	TABLET, FILM COATED	400 mg	ORAL	NDA	30 sections
Multaq	HUMAN PRESCRIPTION DRUG LABEL	1	55154-8104	TABLET, FILM COATED	400 mg	ORAL	NDA	29 sections
Multaq	HUMAN PRESCRIPTION DRUG LABEL	1	55154-8104	TABLET, FILM COATED	400 mg	ORAL	NDA	29 sections