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

Stem definition	Drug id	CAS RN
class III antiarrhythmics	942	115256-11-6

Description:

Molecule	Description
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

Molecule

Description

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:

Property	Value	Reference
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 µM/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
S (Water solubility)	0.02 mg/mL	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company	Orphan
Oct. 1, 1999	FDA	PFIZER

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
Torsade de pointes	204.56	24.74	62	4027	13289	63471644
Electrocardiogram QT prolonged	164.55	24.74	79	4010	59451	63425482
Atrial fibrillation	139.35	24.74	89	4000	116547	63368386
Death	83.53	24.74	111	3978	374270	63110663
Ventricular tachycardia	75.48	24.74	33	4056	19946	63464987
Arrhythmia	65.96	24.74	37	4052	38103	63446830
Palpitations	55.90	24.74	51	4038	112719	63372214
Ventricular fibrillation	46.10	24.74	20	4069	11847	63473086
Cardiac pacemaker insertion	45.79	24.74	15	4074	4111	63480822
Therapy cessation	43.23	24.74	26	4063	30431	63454502
Atrial flutter	43.03	24.74	18	4071	9754	63475179
Cardiac ablation	41.31	24.74	11	4078	1474	63483459
Hospitalisation	39.27	24.74	37	4052	85044	63399889
Heart rate increased	36.07	24.74	37	4052	94201	63390732
Heart rate irregular	34.05	24.74	20	4069	22401	63462532
Cardioversion	33.47	24.74	9	4080	1251	63483682
Dizziness	31.84	24.74	79	4010	429846	63055087
Dyspnoea	31.00	24.74	103	3986	661210	62823723
Blood potassium decreased	26.85	24.74	22	4067	42004	63442929

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
Electrocardiogram QT prolonged	517.64	22.51	192	4075	40760	34911904
Torsade de pointes	165.40	22.51	53	4214	7156	34945508
Ventricular tachycardia	151.88	22.51	71	4196	26508	34926156
Death	95.84	22.51	172	4095	397877	34554787
Atrial fibrillation	89.05	22.51	91	4176	122302	34830362
Palpitations	62.27	22.51	46	4221	39940	34912724
Arrhythmia	57.57	22.51	42	4225	35766	34916898
Ventricular fibrillation	53.78	22.51	34	4233	22920	34929744
Cardiac arrest	45.05	22.51	57	4210	96102	34856562
Product substitution issue	39.83	22.51	21	4246	10074	34942590
Hospitalisation	33.64	22.51	38	4229	56864	34895800
Drug ineffective	32.25	22.51	125	4142	456626	34496038
Cardiac disorder	31.10	22.51	32	4235	43094	34909570
Cardioversion	30.43	22.51	9	4258	926	34951738
Therapy cessation	29.75	22.51	21	4246	16952	34935712
Cardiac ablation	29.09	22.51	9	4258	1079	34951585
Dizziness	26.41	22.51	72	4195	218449	34734215
Ventricular extrasystoles	26.16	22.51	17	4250	11991	34940673
Atrial flutter	24.40	22.51	18	4249	15556	34937108
Heart rate irregular	24.16	22.51	18	4249	15789	34936875
Therapy interrupted	24.13	22.51	17	4250	13680	34938984

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
Electrocardiogram QT prolonged	522.74	20.75	217	6441	90169	79647561
Torsade de pointes	315.09	20.75	100	6558	19212	79718518
Ventricular tachycardia	186.92	20.75	84	6574	41851	79695879
Death	150.83	20.75	209	6449	566305	79171425
Atrial fibrillation	137.27	20.75	121	6537	197765	79539965
Palpitations	94.89	20.75	81	6577	126529	79611201
Ventricular fibrillation	90.69	20.75	47	6611	31879	79705851
Arrhythmia	66.98	20.75	49	6609	61223	79676507
Cardiac arrest	65.25	20.75	76	6582	172020	79565710
Cardiac ablation	59.78	20.75	17	6641	2236	79735494
Atrial flutter	50.62	20.75	28	6630	21597	79716133
Therapy cessation	50.24	20.75	34	6624	37528	79700202
Hospitalisation	44.99	20.75	47	6611	94189	79643541
Dyspnoea	44.23	20.75	164	6494	856861	78880869
Dizziness	41.91	20.75	117	6541	526324	79211406
Heart rate irregular	39.97	20.75	28	6630	32651	79705079
Cardiac failure congestive	39.74	20.75	54	6604	142348	79595382
Cardioversion	38.91	20.75	12	6646	2086	79735644
Heart rate increased	37.10	20.75	48	6610	120676	79617054
Cardiac pacemaker insertion	36.94	20.75	15	6643	5807	79731923
Drug ineffective	35.14	20.75	180	6478	1080733	78656997
Therapy interrupted	34.08	20.75	25	6633	31316	79706414
Product dispensing error	33.32	20.75	18	6640	13245	79724485
Blood potassium decreased	31.24	20.75	28	6630	46484	79691246
Cardiac disorder	29.95	20.75	32	6626	65725	79672005
Product prescribing error	28.18	20.75	26	6632	44787	79692943
Product substitution issue	26.28	20.75	18	6640	20238	79717492
Cardiac flutter	25.51	20.75	11	6647	4943	79732787
Surgery	24.56	20.75	21	6637	32745	79704985
Extrasystoles	24.20	20.75	12	6646	7407	79730323
Electrocardiogram T wave biphasic	23.92	20.75	5	6653	180	79737550
Hypoacusis	21.94	20.75	19	6639	30131	79707599

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
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 | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
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

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN	BLOCKER	Ki	8.19	CHEMBL	CHEMBL
Potassium channel subfamily K member 2	Ion channel	O95069	KCNK2_HUMAN				WOMBAT-PK
Potassium voltage-gated channel subfamily H member 1	Ion channel	O95259	KCNH1_HUMAN	BLOCKER	IC50	7.50	IUPHAR

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Tikosyn	HUMAN PRESCRIPTION DRUG LABEL	1	0069-5800	CAPSULE	0.13 mg	ORAL	NDA	25 sections
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	0069-5810	CAPSULE	0.25 mg	ORAL	NDA	25 sections
Tikosyn	HUMAN PRESCRIPTION DRUG LABEL	1	0069-5820	CAPSULE	0.50 mg	ORAL	NDA	25 sections
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	16714-840	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	16714-841	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	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	42291-411	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	42291-412	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	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	42794-044	CAPSULE	125 ug	ORAL	ANDA	24 sections
Dofetilide	HUMAN PRESCRIPTION DRUG LABEL	1	42794-045	CAPSULE	250 ug	ORAL	ANDA	24 sections