dofetilide ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
class III antiarrhythmics, sematilide derivatives 942 115256-11-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • UK 68798
  • dofetilide
  • tikosyn
  • UK-68,798
Dofetilide show Vaughan Williams Class III antiarrhythmic activity. The mechanism of action is blockade of the cardiac ion channel carrying the rapid component of the delayed rectifier potassium current, IKr. At concentrations covering several orders of magnitude, dofetilide blocks only IKr with no relevant block of the other repolarizing potassium currents (e.g., IKs, IK1). At clinically relevant concentrations, dofetilide has no effect on sodium channels (associated with Class I effect), adrenergic alpha-receptors, or adrenergic beta-receptors.
  • Molecular weight: 441.56
  • Formula: C19H27N3O5S2
  • CLOGP: 1.99
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 2
  • TPSA: 104.81
  • ALOGS: -4.35
  • ROTB: 9

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 64 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.04 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 96 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 3.30 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 5.20 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.36 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 8.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Oct. 1, 1999 FDA PFIZER

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
Torsade de pointes 192.65 23.64 60 3833 11775 50589456
Electrocardiogram QT prolonged 155.57 23.64 77 3816 51809 50549422
Atrial fibrillation 121.54 23.64 83 3810 101662 50499569
Ventricular tachycardia 73.96 23.64 32 3861 15789 50585442
Death 68.53 23.64 103 3790 325276 50275955
Arrhythmia 62.02 23.64 36 3857 33096 50568135
Palpitations 53.92 23.64 50 3843 94456 50506775
Ventricular fibrillation 44.93 23.64 20 3873 10539 50590692
Cardiac pacemaker insertion 41.02 23.64 14 3879 3639 50597592
Cardiac ablation 40.87 23.64 11 3882 1283 50599948
Atrial flutter 38.58 23.64 17 3876 8746 50592485
Hospitalisation 36.90 23.64 35 3858 67902 50533329
Dizziness 33.86 23.64 79 3814 346290 50254941
Heart rate increased 33.11 23.64 35 3858 77215 50524016
Therapy cessation 32.80 23.64 22 3871 25989 50575242
Cardioversion 32.74 23.64 9 3884 1136 50600095
Heart rate irregular 30.91 23.64 19 3874 19341 50581890
Dyspnoea 29.90 23.64 101 3792 547507 50053724
Blood potassium decreased 25.91 23.64 22 3871 36923 50564308

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
Electrocardiogram QT prolonged 464.53 21.72 177 3879 35960 29534511
Ventricular tachycardia 142.60 21.72 67 3989 22507 29547964
Torsade de pointes 135.44 21.72 46 4010 6615 29563856
Death 92.47 21.72 166 3890 341918 29228553
Atrial fibrillation 85.91 21.72 88 3968 105558 29464913
Ventricular fibrillation 59.09 21.72 33 4023 15800 29554671
Palpitations 58.99 21.72 43 4013 32561 29537910
Arrhythmia 49.29 21.72 38 4018 31275 29539196
Product substitution issue 39.42 21.72 21 4035 9151 29561320
Hospitalisation 34.89 21.72 37 4019 45951 29524520
Drug ineffective 32.43 21.72 116 3940 363054 29207417
Cardiac ablation 31.76 21.72 9 4047 708 29569763
Cardioversion 30.36 21.72 9 4047 830 29569641
Cardiac disorder 30.08 21.72 31 4025 37232 29533239
Therapy interrupted 29.97 21.72 17 4039 8369 29562102
Cardiac arrest 28.71 21.72 46 4010 85545 29484926
Dizziness 27.58 21.72 72 3984 189612 29380859
Heart rate irregular 25.29 21.72 18 4038 13099 29557372
Atrial flutter 24.36 21.72 18 4038 13876 29556595
Ventricular extrasystoles 23.88 21.72 16 4040 10566 29559905
Condition aggravated 23.81 21.72 58 3998 146237 29424234
Therapy cessation 23.72 21.72 18 4038 14444 29556027
Chronic obstructive pulmonary disease 22.66 21.72 28 4028 40927 29529544

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
Electrocardiogram QT prolonged 458.33 21.29 199 6068 79249 64413216
Torsade de pointes 274.22 21.29 91 6176 17272 64475193
Ventricular tachycardia 174.96 21.29 79 6188 34186 64458279
Death 132.99 21.29 196 6071 482509 64009956
Atrial fibrillation 122.88 21.29 114 6153 170975 64321490
Ventricular fibrillation 93.91 21.29 46 6221 23814 64468651
Palpitations 89.52 21.29 77 6190 104411 64388054
Cardiac ablation 61.27 21.29 17 6250 1755 64490710
Arrhythmia 57.87 21.29 45 6222 52899 64439566
Therapy cessation 50.04 21.29 34 6233 32455 64460010
Atrial flutter 46.83 21.29 27 6240 19353 64473112
Dizziness 45.69 21.29 117 6150 430046 64062419
Hospitalisation 44.22 21.29 45 6222 75162 64417303
Cardiac arrest 44.15 21.29 64 6203 154000 64338465
Dyspnoea 43.15 21.29 160 6107 718514 63773951
Therapy interrupted 40.81 21.29 25 6242 20011 64472454
Cardioversion 38.38 21.29 12 6255 1873 64490592
Heart rate irregular 38.25 21.29 27 6240 27386 64465079
Drug ineffective 36.96 21.29 170 6097 840077 63652388
Cardiac pacemaker insertion 36.89 21.29 15 6252 5008 64487457
Heart rate increased 35.83 21.29 46 6221 98629 64393836
Cardiac failure congestive 34.16 21.29 52 6215 130528 64361937
Blood potassium decreased 27.12 21.29 26 6241 40373 64452092
Cardiac disorder 26.79 21.29 30 6237 55786 64436679
Product substitution issue 25.86 21.29 18 6249 17843 64474622
Cardiac flutter 25.68 21.29 11 6256 4178 64488287
Surgery 24.53 21.29 21 6246 28192 64464273
Extrasystoles 23.70 21.29 12 6255 6646 64485819
Electrocardiogram T wave biphasic 23.16 21.29 5 6262 180 64492285
Product dispensing error 22.58 21.29 14 6253 11436 64481029
Product prescribing error 22.36 21.29 22 6245 35247 64457218

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C01BD04 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
ANTIARRHYTHMICS, CLASS I AND III
Antiarrhythmics, class III
FDA EPC N0000175426 Antiarrhythmic
CHEBI has role CHEBI:38070 antiarrhythmic agent
MeSH PA D000889 Anti-Arrhythmia Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D026902 Potassium Channel Blockers

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Atrial fibrillation indication 49436004 DOID:0060224
Cardioversion of Atrial Fibrillation indication
Cardioversion of Atrial Flutter indication
Torsades de pointes contraindication 31722008
Hypokalemia contraindication 43339004
Anorexia nervosa contraindication 56882008 DOID:8689
Acute nephropathy contraindication 58574008
Kidney disease contraindication 90708001 DOID:557
Prolonged QT interval contraindication 111975006
Hypomagnesemia contraindication 190855004
Disease of liver contraindication 235856003 DOID:409
Hyperhidrosis contraindication 312230002
Severe diarrhea contraindication 409587002
Vomiting contraindication 422400008
Congenital long QT syndrome contraindication 442917000




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.4 acidic
pKa2 9.16 acidic
pKa3 8.0 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 voltage-gated channel subfamily H member 2 Ion channel BLOCKER Ki 8.19 CHEMBL CHEMBL
Potassium channel subfamily K member 2 Ion channel WOMBAT-PK
Potassium voltage-gated channel subfamily H member 1 Ion channel BLOCKER IC50 7.50 IUPHAR

External reference:

IDSource
4021202 VUID
N0000148648 NUI
D00647 KEGG_DRUG
261672 RXNORM
4021202 VANDF
C0114771 UMLSCUI
CHEBI:4681 CHEBI
CHEMBL473 ChEMBL_ID
DB00204 DRUGBANK_ID
C063533 MESH_SUPPLEMENTAL_RECORD_UI
2604 IUPHAR_LIGAND_ID
6756 INN_ID
R4Z9X1N2ND UNII
71329 PUBCHEM_CID
241646 MMSL
31824 MMSL
8476 MMSL
d04459 MMSL
007996 NDDF
116107002 SNOMEDCT_US
392658005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Tikosyn HUMAN PRESCRIPTION DRUG LABEL 1 0069-5800 CAPSULE 0.13 mg ORAL NDA 25 sections
Tikosyn HUMAN PRESCRIPTION DRUG LABEL 1 0069-5810 CAPSULE 0.25 mg ORAL NDA 25 sections
Tikosyn HUMAN PRESCRIPTION DRUG LABEL 1 0069-5820 CAPSULE 0.50 mg ORAL NDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 0904-6681 CAPSULE 0.13 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 0904-6682 CAPSULE 0.25 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 0904-6683 CAPSULE 0.50 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 16714-840 CAPSULE 0.13 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 16714-841 CAPSULE 0.25 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 16714-842 CAPSULE 0.50 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 16729-490 CAPSULE 0.13 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 16729-490 CAPSULE 0.13 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 16729-491 CAPSULE 0.25 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 16729-491 CAPSULE 0.25 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 16729-492 CAPSULE 0.50 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 16729-492 CAPSULE 0.50 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 42291-411 CAPSULE 125 ug ORAL ANDA 24 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 42291-412 CAPSULE 250 ug ORAL ANDA 24 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 42291-413 CAPSULE 500 ug ORAL ANDA 24 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 42794-044 CAPSULE 125 ug ORAL ANDA 24 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 42794-045 CAPSULE 250 ug ORAL ANDA 24 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 42794-046 CAPSULE 500 ug ORAL ANDA 24 sections
DOFETILIDE Human Prescription Drug Label 1 47335-061 CAPSULE 0.13 mg ORAL ANDA 23 sections
DOFETILIDE Human Prescription Drug Label 1 47335-062 CAPSULE 0.25 mg ORAL ANDA 23 sections
DOFETILIDE Human Prescription Drug Label 1 47335-063 CAPSULE 0.50 mg ORAL ANDA 23 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 51862-005 CAPSULE 0.50 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 51862-025 CAPSULE 0.25 mg ORAL ANDA 25 sections
Dofetilide HUMAN PRESCRIPTION DRUG LABEL 1 51862-125 CAPSULE 0.13 mg ORAL ANDA 25 sections
Dofetilide Human Prescription Drug Label 1 59651-118 CAPSULE 0.13 mg ORAL ANDA 23 sections
Dofetilide Human Prescription Drug Label 1 59651-119 CAPSULE 0.25 mg ORAL ANDA 23 sections
Dofetilide Human Prescription Drug Label 1 59651-120 CAPSULE 0.50 mg ORAL ANDA 23 sections