dronedarone 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
antiarrhythmics 4112 141626-36-0

Description:

MoleculeDescription

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:

DoseUnitRoute
0.80 g O

ADMET properties:

PropertyValueReference
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
BA (Bioavailability) 15 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.621 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 4.395 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 2.388 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 13.964 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.280 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 1.120 % High 1
herg hERG pIC50 6.011 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 36.813 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 239.883 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.250 % High 1
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AKT1,AKT2,AKT3,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,INSR,ITK,JAK1,JAK2,JAK3,KDR,KIT,MAP2K6,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAPK10,MAPK12,MAPK7,MAPK9,MAPKAPK2,MARK4,MELK,MET,MTOR,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CB,PIM2,PLK1,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ULK1 64
kinase-selectivity-class AXL,CAMK2D,CDK4,EIF2AK3,EPHB4,ERBB2,GRK2,INSR,MAP2K6,MAPK7,PDK4,PRKCD,SIK2,STK33,TEK 15
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 5.152 High 1
mh-clint Mouse hepatocyte intrinsic clearance 112.980 High 1
mppb Mouse plasma protein binding (% unbound) 0.280 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 11.246 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 High 1
pppb Pig plasma protein binding (% unbound) 0.630 % High 1
rh-clint Rat hepatocyte intrinsic clearance 98.628 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 0.740 % High 1
rppb Rat plasma protein binding (% unbound) 0.230 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 1.892 uM High 1

Approvals:

DateAgencyCompanyOrphan
July 1, 2009 FDA SANOFI AVENTIS US

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Atrial fibrillation 220.88 22.32 132 6586 133479 90488250
Blood creatinine increased 201.63 22.32 113 6605 101273 90520456
Drug interaction 197.03 22.32 163 6555 276290 90345439
International normalised ratio increased 146.40 22.32 71 6647 47245 90574484
Dyspnoea 123.11 22.32 227 6491 880728 89741001
Torsade de pointes 111.27 22.32 42 6676 15140 90606589
Cardiac failure 106.98 22.32 78 6640 109418 90512311
Cardiac failure congestive 97.98 22.32 71 6647 98623 90523106
Gastrointestinal haemorrhage 85.21 22.32 63 6655 90185 90531544
Hepatocellular injury 70.58 22.32 37 6681 28921 90592808
Renal failure 70.43 22.32 66 6652 130941 90490788
Ventricular tachycardia 70.17 22.32 35 6683 24673 90597056
Glomerular filtration rate decreased 66.54 22.32 30 6688 16902 90604827
Alanine aminotransferase increased 66.27 22.32 61 6657 118277 90503452
Subchondral insufficiency fracture 59.83 22.32 9 6709 49 90621680
Aspartate aminotransferase increased 57.51 22.32 53 6665 102884 90518845
Palpitations 57.02 22.32 60 6658 136668 90485061
Arrhythmia 52.63 22.32 35 6683 42297 90579432
Atrial flutter 48.52 22.32 21 6697 10737 90610992
Bradycardia 46.49 22.32 43 6675 83804 90537925
Gamma-glutamyltransferase increased 46.26 22.32 31 6687 37921 90583808
Electrocardiogram R on T phenomenon 35.62 22.32 5 6713 15 90621714
Acute kidney injury 34.04 22.32 74 6644 320313 90301416
Liver function test abnormal 33.99 22.32 29 6689 50816 90570913
Oedema peripheral 33.82 22.32 65 6653 257850 90363879
Blood bilirubin increased 31.55 22.32 26 6692 43444 90578285
Blood alkaline phosphatase increased 31.28 22.32 27 6691 48052 90573677
Transaminases increased 30.73 22.32 24 6694 37168 90584561
Ventricular fibrillation 28.78 22.32 16 6702 14028 90607701
Brain natriuretic peptide increased 27.99 22.32 12 6706 5993 90615736
Hyperthyroidism 27.35 22.32 17 6701 18293 90603436
Atrioventricular block first degree 26.98 22.32 13 6705 8498 90613231
Pulmonary oedema 25.41 22.32 27 6691 62053 90559676
Product residue present 24.81 22.32 10 6708 4281 90617448
Blood urea increased 23.78 22.32 19 6699 30394 90591335
Electrocardiogram QT prolonged 23.64 22.32 28 6690 72428 90549301
Sinus arrest 23.51 22.32 8 6710 2138 90619591
Hepatic failure 23.22 22.32 21 6697 39707 90582022
Gastroenteritis clostridial 22.77 22.32 6 6712 669 90621060
Jaundice 22.66 22.32 19 6699 32498 90589231

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Atrial fibrillation 143.63 21.73 135 5985 139458 42475757
Blood creatinine increased 142.07 21.73 121 5999 109882 42505333
Drug interaction 108.16 21.73 160 5960 266839 42348376
Dyspnoea 106.33 21.73 210 5910 442411 42172804
International normalised ratio increased 92.36 21.73 67 6053 48101 42567114
Ventricular tachycardia 89.33 21.73 55 6065 30105 42585110
Cardiac failure 66.14 21.73 79 6041 106777 42508438
Gastrointestinal haemorrhage 63.37 21.73 74 6046 97652 42517563
Cardiac failure congestive 52.46 21.73 63 6057 85539 42529676
Atrial flutter 49.88 21.73 31 6089 17220 42597995
Glomerular filtration rate decreased 46.31 21.73 29 6091 16322 42598893
Bradycardia 46.08 21.73 59 6061 85425 42529790
Ventricular fibrillation 42.58 21.73 35 6085 30088 42585127
Hyperthyroidism 42.04 21.73 26 6094 14315 42600900
Cholangitis sclerosing 41.41 21.73 14 6106 1888 42613327
Arrhythmia 41.28 21.73 39 6081 40278 42574937
Electrocardiogram QT prolonged 40.94 21.73 42 6078 47903 42567312
Xanthopsia 38.65 21.73 8 6112 156 42615059
Creatinine renal clearance decreased 32.67 21.73 14 6106 3599 42611616
Torsade de pointes 31.50 21.73 18 6102 8576 42606639
Liver function test abnormal 28.78 21.73 29 6091 32362 42582853
Cardiac ablation 26.14 21.73 9 6111 1281 42613934
Palpitations 25.69 21.73 34 6086 50763 42564452
Hepatic enzyme increased 25.27 21.73 32 6088 45752 42569463
Sinoatrial block 24.80 21.73 7 6113 518 42614697
Blood loss anaemia 24.42 21.73 16 6104 9720 42605495
Alanine aminotransferase increased 23.47 21.73 44 6076 88362 42526853
Gamma-glutamyltransferase increased 23.37 21.73 26 6094 32471 42582744
Dizziness 22.79 21.73 83 6037 249171 42366044
Underdose 22.78 21.73 19 6101 16647 42598568
Hepatocellular injury 22.51 21.73 22 6098 23656 42591559

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Blood creatinine increased 282.26 19.26 193 10816 182696 110395594
Drug interaction 280.59 19.26 294 10715 499889 110078401
Atrial fibrillation 245.06 19.26 194 10815 229448 110348842
International normalised ratio increased 184.11 19.26 112 10897 86660 110491630
Dyspnoea 181.70 19.26 362 10647 1106510 109471780
Gastrointestinal haemorrhage 133.24 19.26 119 10890 165399 110412891
Cardiac failure congestive 120.40 19.26 108 10901 150892 110427398
Torsade de pointes 104.32 19.26 49 10960 22551 110555739
Cardiac failure 100.56 19.26 108 10901 187518 110390772
Ventricular tachycardia 96.97 19.26 61 10948 49948 110528342
Glomerular filtration rate decreased 87.17 19.26 47 10962 28909 110549381
Hepatocellular injury 83.99 19.26 56 10953 50586 110527704
Alanine aminotransferase increased 78.41 19.26 94 10915 183679 110394611
Bradycardia 77.17 19.26 86 10923 155431 110422859
Ventricular fibrillation 76.61 19.26 49 10960 41264 110537026
Atrial flutter 71.97 19.26 39 10970 24223 110554067
Palpitations 68.82 19.26 82 10927 159130 110419160
Aspartate aminotransferase increased 68.52 19.26 82 10927 159854 110418436
Gamma-glutamyltransferase increased 65.61 19.26 52 10957 61257 110517033
Renal failure 58.70 19.26 91 10918 226483 110351807
Arrhythmia 57.84 19.26 51 10958 69524 110508766
Subchondral insufficiency fracture 57.02 19.26 9 11000 50 110578240
Hyperthyroidism 52.50 19.26 34 10975 29227 110549063
Electrocardiogram QT prolonged 46.86 19.26 56 10953 108904 110469386
Cardiac ablation 37.79 19.26 13 10996 2669 110575621
Cholangitis sclerosing 37.75 19.26 14 10995 3568 110574722
Blood bilirubin increased 37.62 19.26 42 10967 75930 110502360
Blood loss anaemia 37.48 19.26 23 10986 18002 110560288
Oedema peripheral 37.04 19.26 93 10916 328567 110249723
Blood alkaline phosphatase increased 36.48 19.26 40 10969 70895 110507395
Liver function test abnormal 35.67 19.26 39 10970 68911 110509379
Xanthopsia 34.98 19.26 8 11001 367 110577923
Sinus bradycardia 33.68 19.26 26 10983 29457 110548833
Dizziness 33.65 19.26 148 10861 698045 109880245
Brain natriuretic peptide increased 33.18 19.26 18 10991 11191 110567099
Transaminases increased 33.04 19.26 36 10973 63354 110514936
Extrasystoles 32.22 19.26 16 10993 8302 110569988
Acute kidney injury 31.60 19.26 136 10873 635294 109942996
Jaundice 31.50 19.26 34 10975 59202 110519088
Blood urea increased 28.27 19.26 31 10978 54926 110523364
Ventricular extrasystoles 28.14 19.26 21 10988 22620 110555670
Haemorrhage 27.80 19.26 43 10966 106649 110471641
Infusion related reaction 27.39 19.26 3 11006 381159 110197131
Electrocardiogram R on T phenomenon 26.85 19.26 4 11005 14 110578276
Atrioventricular block second degree 26.64 19.26 14 10995 8167 110570123
Cholestatic liver injury 25.10 19.26 13 10996 7363 110570927
Neutropenia 24.41 19.26 4 11005 374616 110203674
Atrioventricular block first degree 24.22 19.26 16 10993 14209 110564081
Tachycardia 23.31 19.26 62 10947 226583 110351707
Underdose 23.05 19.26 30 10979 63524 110514766
Melaena 22.70 19.26 31 10978 68726 110509564
Pain 22.37 19.26 38 10971 954917 109623373
Sudden cardiac death 22.30 19.26 11 10998 5626 110572664
Sinus arrest 22.07 19.26 10 10999 4232 110574058
Hepatitis toxic 21.79 19.26 11 10998 5910 110572380
Atrioventricular block 21.75 19.26 16 10993 16861 110561429
Haemorrhage intracranial 21.63 19.26 20 10989 28949 110549341
Hepatic failure 21.21 19.26 30 10979 68709 110509581
Pulmonary toxicity 21.03 19.26 16 10993 17730 110560560
Coagulopathy 20.91 19.26 23 10986 40888 110537402
Pulmonary oedema 20.09 19.26 36 10973 100623 110477667
Cardiac tamponade 19.94 19.26 13 10996 11294 110566996
Acute pulmonary oedema 19.43 19.26 15 10994 16981 110561309

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
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:35554 cardiovascular drug
CHEBI has role CHEBI:35703 xenobiotic
CHEBI has role CHEBI:38070 anti-arrhythmia drug
CHEBI has role CHEBI:78298 environmental contaminant

Related Drugs by ATC class:

C01BD Antiarrhythmics, class III 6 drugs
amiodaronebretyliumbunaftinedofetilideibutilidetedisamil

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

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (acidic/basic)
pKa1 7.65 acidic
pKa2 9.7 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent 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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Ion channel BLOCKER SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Ion channel BLOCKER SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 Ion channel BLOCKER SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Ion channel BLOCKER SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Potassium voltage-gated channel subfamily A member 5 Ion channel IC50 5.63 CHEMBL
Thyroid hormone receptor alpha Nuclear hormone receptor IC50 4.23 WOMBAT-PK
THAP domain-containing protein 1 Transcription factor IC50 4.23 WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 6.50 CHEMBL
Voltage-dependent calcium channel gamma-1 subunit Ion channel IC50 6.70 WOMBAT-PK
Potassium voltage-gated channel subfamily KQT member 2 Ion channel BLOCKER IC50 8 WOMBAT-PK
NACHT, LRR and PYD domains-containing protein 3 Cytosolic other IC50 5.17 CHEMBL

External reference:

IDSource
4028918 VUID
N0000179804 NUI
D02537 KEGG_DRUG
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
141625-93-6 SECONDARY_CAS_RN
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
JQZ1L091Y2 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Multaq HUMAN PRESCRIPTION DRUG LABEL 1 0024-4142 TABLET, FILM COATED 400 mg ORAL NDA 34 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 34 sections