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

Stem definition	Drug id	CAS RN
class III antiarrhythmics, sematilide derivatives	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

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	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 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	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 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	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:

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	0069-5810	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