dronedarone Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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 ┬ÁM/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:

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 607.32 21.57 291 6127 103299 46576345
Cardiac failure 173.98 21.57 118 6300 79830 46599814
Blood creatinine increased 166.78 21.57 113 6305 76290 46603354
International normalised ratio increased 146.38 21.57 87 6331 46796 46632848
Drug interaction 143.36 21.57 157 6261 202937 46476707
Dyspnoea 93.86 21.57 213 6205 515335 46164309
Torsade de pointes 92.00 21.57 41 6377 12113 46667531
Cardiac failure congestive 73.42 21.57 76 6342 91674 46587970
Glomerular filtration rate decreased 65.39 21.57 32 6386 11662 46667982
Ventricular tachycardia 64.94 21.57 36 6382 16931 46662713
Gastrointestinal haemorrhage 59.92 21.57 63 6355 77310 46602334
Hepatocellular injury 55.68 21.57 40 6378 29482 46650162
Subchondral insufficiency fracture 53.25 21.57 9 6409 56 46679588
Alanine aminotransferase increased 53.00 21.57 63 6355 88388 46591256
Aspartate aminotransferase increased 45.40 21.57 55 6363 78645 46600999
Renal failure 42.08 21.57 64 6354 113530 46566114
Arrhythmia 37.49 21.57 34 6384 34807 46644837
Palpitations 37.16 21.57 55 6363 95204 46584440
Gamma-glutamyltransferase increased 36.18 21.57 32 6386 31708 46647936
Atrial flutter 33.87 21.57 19 6399 9129 46670515
Electrocardiogram R on T phenomenon 31.62 21.57 5 6413 19 46679625
Bradycardia 29.85 21.57 41 6377 66257 46613387
Ischaemic stroke 27.78 21.57 21 6397 16701 46662943
Acute kidney injury 26.70 21.57 82 6336 235773 46443871
Hyperthyroidism 24.70 21.57 17 6401 11694 46667950
Oedema peripheral 24.45 21.57 62 6356 159644 46520000
Rectal haemorrhage 24.12 21.57 28 6390 38227 46641417
Transaminases increased 23.98 21.57 24 6394 27737 46651907
Blood bilirubin increased 23.21 21.57 26 6392 34158 46645486
Hepatitis acute 22.39 21.57 14 6404 8200 46671444

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 496.22 22.38 297 5975 107827 29838379
Cardiac failure 202.37 22.38 155 6117 83263 29862943
Blood creatinine increased 139.21 22.38 130 6142 91245 29854961
Drug interaction 106.01 22.38 166 6106 199402 29746804
Ventricular tachycardia 96.88 22.38 61 6211 23801 29922405
International normalised ratio increased 92.62 22.38 78 6194 47661 29898545
Dyspnoea 84.97 22.38 203 6069 333092 29613114
Bradycardia 61.35 22.38 72 6200 65454 29880752
Gastrointestinal haemorrhage 53.47 22.38 76 6196 83370 29862836
Electrocardiogram QT prolonged 48.71 22.38 48 6224 35787 29910419
Cholangitis sclerosing 46.21 22.38 14 6258 906 29945300
Glomerular filtration rate decreased 45.95 22.38 29 6243 11333 29934873
Cardiac failure congestive 44.24 22.38 70 6202 84337 29861869
Arrhythmia 42.44 22.38 43 6229 33126 29913080
Atrial flutter 42.22 22.38 30 6242 14251 29931955
Hyperthyroidism 41.33 22.38 24 6248 8074 29938132
Ventricular fibrillation 40.65 22.38 30 6242 15108 29931098
Torsade de pointes 38.54 22.38 22 6250 7168 29939038
Xanthopsia 35.41 22.38 8 6264 161 29946045
Hepatic enzyme increased 35.01 22.38 39 6233 33455 29912751
Cardiac death 32.44 22.38 11 6261 1022 29945184
Creatinine renal clearance decreased 28.46 22.38 14 6258 3379 29942827
Ventricular extrasystoles 26.96 22.38 21 6251 11453 29934753
Liver function test abnormal 24.05 22.38 31 6241 30919 29915287
Alanine aminotransferase increased 24.04 22.38 50 6222 74226 29871980
Palpitations 23.58 22.38 32 6240 33541 29912665
Sinoatrial block 23.18 22.38 7 6265 448 29945758
Syncope 22.77 22.38 53 6219 84850 29861356
Blood loss anaemia 22.48 22.38 16 6256 7611 29938595

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:35703 xenobiotic
CHEBI has role CHEBI:38070 antiarrhythmic agent
CHEBI has role CHEBI:78298 environmental contaminants

Drug Use (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

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)

None

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 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/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Ion channel BLOCKER SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
THAP domain-containing protein 1 Unclassified IC50 4.23 WOMBAT-PK
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
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 6.50 CHEMBL
Potassium voltage-gated channel subfamily KQT member 2 Ion channel BLOCKER IC50 8 WOMBAT-PK
Voltage-dependent calcium channel gamma-1 subunit Ion channel IC50 6.70 WOMBAT-PK

External reference:

IDSource
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
DB04855 DRUGBANK_ID
D000077764 MESH_DESCRIPTOR_UI
208898 PUBCHEM_CID
7465 IUPHAR_LIGAND_ID
7382 INN_ID
JQZ1L091Y2 UNII
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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