Identification
- Summary
Dofetilide is a class III antiarrhythmic drug used for the maintenance of normal sinus rhythm and cardioversion in cases of atrial fibrillation and atrial flutter.
- Brand Names
- Tikosyn
- Generic Name
- Dofetilide
- DrugBank Accession Number
- DB00204
- Background
Dofetilide is a class III antiarrhythmic agent that is approved by the Food and Drug Administration (FDA) for the maintenance of sinus rhythm in individuals prone to the formation of atrial fibrillation and flutter, and for the chemical cardioversion to sinus rhythm from atrial fibrillation and flutter.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Dofetilide (DB00204)
- Weight
- Average: 441.565
Monoisotopic: 441.139212369 - Chemical Formula
- C19H27N3O5S2
- Synonyms
- beta-((p-Methanesulfonamidophenethyl)methylamino)methanesulfono-p-phenetidide
- Dofetilida
- Dofetilide
- Dofetilidum
- External IDs
- UK-68,798
- UK-68798
Pharmacology
- Indication
For the maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter [AF/AFl]) in patients with atrial fibrillation/atrial flutter of greater than one week duration who have been converted to normal sinus rhythm
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Dofetilide is an antiarrhythmic drug with Class III (cardiac action potential duration prolonging) properties and is indicated for the maintenance of normal sinus rhythm. Dofetilide increases the monophasic action potential duration in a predictable, concentration-dependent manner, primarily due to delayed repolarization. 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.
- Mechanism of action
The mechanism of action of Dofetilide is a blockade of the cardiac ion channel carrying the rapid component of the delayed rectifier potassium current, IKr. This inhibition of potassium channels results in a prolongation of action potential duration and the effective refractory period of accessory pathways (both anterograde and retrograde conduction in the accessory pathway).
Target Actions Organism APotassium voltage-gated channel subfamily H member 2 inhibitorHumans APotassium channel subfamily K member 2 inhibitorHumans AATP-sensitive inward rectifier potassium channel 12 inhibitorHumans - Absorption
>90%
- Volume of distribution
- 3 L/kg
- Protein binding
60% -70%
- Metabolism
Hepatic
- Route of elimination
Not Available
- Half-life
10 hours
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Dofetilide can be increased when it is combined with Abametapir. Abatacept The metabolism of Dofetilide can be increased when combined with Abatacept. Acalabrutinib The metabolism of Dofetilide can be decreased when combined with Acalabrutinib. Acebutolol Dofetilide may increase the arrhythmogenic activities of Acebutolol. Acetaminophen The metabolism of Dofetilide can be increased when combined with Acetaminophen. Acetazolamide The metabolism of Dofetilide can be decreased when combined with Acetazolamide. Acetyldigitoxin Dofetilide may increase the arrhythmogenic activities of Acetyldigitoxin. Acrivastine The risk or severity of QTc prolongation can be increased when Acrivastine is combined with Dofetilide. Adagrasib The metabolism of Dofetilide can be decreased when combined with Adagrasib. Adalimumab The metabolism of Dofetilide can be increased when combined with Adalimumab. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of dofetilide.
- Exercise caution with St. John's Wort. Dofetilide is partially metabolized by CYP3A4, and St. John's Wort is a CYP3A4 inducer, coadministration may reduce dofetilide serum levels.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Dofetilide Capsule 0.125 mg/1 Oral Greenstone LLC 2016-05-01 2021-03-31 US 
Dofetilide Capsule 0.5 mg/1 Oral Greenstone LLC 2016-05-01 2021-03-31 US Dofetilide Capsule 0.25 mg/1 Oral Greenstone LLC 2016-05-01 2021-03-31 US Tikosyn Capsule 0.5 mg/1 Oral Avera McKennan Hospital 2016-03-28 Not applicable US Tikosyn Capsule 0.5 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 1999-10-01 Not applicable US Tikosyn Capsule 0.25 mg/1 Oral Avera McKennan Hospital 2016-07-29 Not applicable US Tikosyn Capsule 0.25 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 1999-10-01 Not applicable US 
Tikosyn Capsule 0.125 mg/1 Oral Avera McKennan Hospital 2016-06-28 Not applicable US Tikosyn Capsule 0.125 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 1999-10-01 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Dofetilide Capsule 0.125 mg/1 Oral Liberty Bioscience LLC 2016-06-07 Not applicable US Dofetilide Capsule 0.5 mg/1 Oral Aurobindo Pharma Limited 2019-01-22 Not applicable US Dofetilide Capsule 0.5 mg/1 Oral NorthStar Rx LLC 2018-06-18 Not applicable US Dofetilide Capsule 0.250 mg/1 Oral Msn Laboratories Private Limited 2020-01-29 Not applicable US Dofetilide Capsule 0.125 mg/1 Oral VGYAAN Pharmaceuticals LLC 2022-10-25 Not applicable US Dofetilide Capsule 125 ug/1 Oral AvKARE 2018-08-06 Not applicable US Dofetilide Capsule 0.5 mg/1 Oral Mayne Pharma Inc. 2016-06-07 Not applicable US Dofetilide Capsule 0.25 mg/1 Oral Ingenus Pharmaceuticals, LLC 2020-01-07 Not applicable US Dofetilide Capsule 0.25 mg/1 Oral Bionpharma Inc. 2018-04-11 Not applicable US Dofetilide Capsule 0.125 mg/1 Oral Major Pharmaceuticals 2016-06-07 Not applicable US
Categories
- ATC Codes
- C01BD04 — Dofetilide
- Drug Categories
- Amides
- Amines
- Antiarrhythmic agents
- Antiarrhythmics, Class III
- Cardiac Therapy
- Cardiovascular Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Ethylamines
- Highest Risk QTc-Prolonging Agents
- Membrane Transport Modulators
- Narrow Therapeutic Index Drugs
- OCT2 Substrates
- OCT2 Substrates with a Narrow Therapeutic Index
- Potassium Channel Blockers
- QTc Prolonging Agents
- Sulfones
- Sulfur Compounds
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as sulfanilides. These are organic aromatic compounds containing a sulfanilide moiety, with the general structure RS(=O)(=O)NC1=CC=CC=C1.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Sulfanilides
- Direct Parent
- Sulfanilides
- Alternative Parents
- Phenethylamines / Phenoxy compounds / Phenol ethers / Aralkylamines / Alkyl aryl ethers / Organosulfonamides / Organic sulfonamides / Aminosulfonyl compounds / Trialkylamines / Organopnictogen compounds show 2 more
- Substituents
- Alkyl aryl ether / Amine / Aminosulfonyl compound / Aralkylamine / Aromatic homomonocyclic compound / Ether / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide / Organic oxygen compound show 15 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- tertiary amino compound, aromatic ether, sulfonamide (CHEBI:4681)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- R4Z9X1N2ND
- CAS number
- 115256-11-6
- InChI Key
- IXTMWRCNAAVVAI-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H27N3O5S2/c1-22(13-12-16-4-6-17(7-5-16)20-28(2,23)24)14-15-27-19-10-8-18(9-11-19)21-29(3,25)26/h4-11,20-21H,12-15H2,1-3H3
- IUPAC Name
- N-[4-(2-{[2-(4-methanesulfonamidophenoxy)ethyl](methyl)amino}ethyl)phenyl]methanesulfonamide
- SMILES
- CN(CCOC1=CC=C(NS(C)(=O)=O)C=C1)CCC1=CC=C(NS(C)(=O)=O)C=C1
References
- Synthesis Reference
- US4959366
- General References
- Lenz TL, Hilleman DE: Dofetilide, a new class III antiarrhythmic agent. Pharmacotherapy. 2000 Jul;20(7):776-86. [Article]
- Lenz TL, Hilleman DE: Dofetilide: A new antiarrhythmic agent approved for conversion and/or maintenance of atrial fibrillation/atrial flutter. Drugs Today (Barc). 2000 Nov;36(11):759-71. [Article]
- Torp-Pedersen C, Moller M, Bloch-Thomsen PE, Kober L, Sandoe E, Egstrup K, Agner E, Carlsen J, Videbaek J, Marchant B, Camm AJ: Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med. 1999 Sep 16;341(12):857-65. [Article]
- External Links
- Human Metabolome Database
- HMDB0014349
- KEGG Drug
- D00647
- KEGG Compound
- C07751
- PubChem Compound
- 71329
- PubChem Substance
- 46509127
- ChemSpider
- 64435
- BindingDB
- 50031720
- 49247
- ChEBI
- 4681
- ChEMBL
- CHEMBL473
- ZINC
- ZINC000000596731
- Therapeutic Targets Database
- DAP000495
- PharmGKB
- PA449389
- Guide to Pharmacology
- GtP Drug Page
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Dofetilide
- FDA label
- Download (1.45 MB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Not Available Paroxysmal Atrial Fibrillation (PAF) 1 4 Withdrawn Treatment Atrial Fibrillation 1 3 Suspended Treatment Atrial Fibrillation 1 3 Terminated Treatment Atrial Fibrillation / Heart Failure 1 1 Completed Basic Science Drug-induced QT Interval Prolongation / Pharmacodynamics / Pharmacokinetics 1 1 Completed Other Drug-induced QT Interval Prolongation / Pharmacodynamics / Pharmacokinetics 1 1 Completed Treatment Drug-induced Surface ECG Changes 1 1 Completed Treatment Long QT Syndrome (LQTS) 1 Not Available Completed Not Available Atrial Fibrillation 1 Not Available Completed Treatment Atrial Fibrillation 1
Pharmacoeconomics
- Manufacturers
- Pfizer pharmaceuticals production corp ltd
- Packagers
- Pfizer Inc.
- Dosage Forms
Form Route Strength Capsule Oral 0.250 mg/1 Capsule Oral 0.500 mg/1 Capsule Oral 125 ug/1 Capsule Oral 250 ug/1 Capsule Oral 500 ug/1 Capsule Oral 0.125 mg/1 Capsule Oral 0.25 mg/1 Capsule Oral 0.5 mg/1 - Prices
Unit description Cost Unit Tikosyn 250 mcg capsule 3.64USD capsule Tikosyn 125 mcg capsule 3.63USD capsule Tikosyn 500 mcg capsule 3.61USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US4959366 No 1990-09-25 2012-09-25 US US6124363 No 2000-09-26 2018-10-09 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 2.1 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0198 mg/mL ALOGPS logP 2.17 ALOGPS logP 0.24 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 10.15 Chemaxon pKa (Strongest Basic) 8.99 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 104.81 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 113.27 m3·mol-1 Chemaxon Polarizability 46.03 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9924 Blood Brain Barrier + 0.9179 Caco-2 permeable - 0.6257 P-glycoprotein substrate Substrate 0.6018 P-glycoprotein inhibitor I Inhibitor 0.6848 P-glycoprotein inhibitor II Non-inhibitor 0.7391 Renal organic cation transporter Non-inhibitor 0.7308 CYP450 2C9 substrate Non-substrate 0.7572 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.6699 CYP450 1A2 substrate Non-inhibitor 0.6359 CYP450 2C9 inhibitor Non-inhibitor 0.5189 CYP450 2D6 inhibitor Non-inhibitor 0.7709 CYP450 2C19 inhibitor Inhibitor 0.544 CYP450 3A4 inhibitor Non-inhibitor 0.7715 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6823 Ames test Non AMES toxic 0.6193 Carcinogenicity Non-carcinogens 0.6038 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.5430 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.8119 hERG inhibition (predictor II) Inhibitor 0.8258
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-0006-1610900000-368db21beef81a5319f4 MS/MS Spectrum - , positive LC-MS/MS splash10-0006-0300900000-47394a7ed027cb5ab3cf
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Potassium voltage-gated channel subfamily H member 2
- Molecular Weight
- 126653.52 Da
References
- Lees-Miller JP, Duan Y, Teng GQ, Duff HJ: Molecular determinant of high-affinity dofetilide binding to HERG1 expressed in Xenopus oocytes: involvement of S6 sites. Mol Pharmacol. 2000 Feb;57(2):367-74. [Article]
- Overholt JL, Ficker E, Yang T, Shams H, Bright GR, Prabhakar NR: HERG-Like potassium current regulates the resting membrane potential in glomus cells of the rabbit carotid body. J Neurophysiol. 2000 Mar;83(3):1150-7. [Article]
- Finlayson K, Pennington AJ, Kelly JS: [3H]dofetilide binding in SHSY5Y and HEK293 cells expressing a HERG-like K+ channel? Eur J Pharmacol. 2001 Feb 2;412(3):203-12. [Article]
- Finlayson K, Turnbull L, January CT, Sharkey J, Kelly JS: [3H]dofetilide binding to HERG transfected membranes: a potential high throughput preclinical screen. Eur J Pharmacol. 2001 Oct 26;430(1):147-8. [Article]
- Ficker E, Jarolimek W, Brown AM: Molecular determinants of inactivation and dofetilide block in ether a-go-go (EAG) channels and EAG-related K(+) channels. Mol Pharmacol. 2001 Dec;60(6):1343-8. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Ficker E, Jarolimek W, Kiehn J, Baumann A, Brown AM: Molecular determinants of dofetilide block of HERG K+ channels. Circ Res. 1998 Feb 23;82(3):386-95. [Article]
- Kang J, Chen XL, Wang H, Ji J, Cheng H, Incardona J, Reynolds W, Viviani F, Tabart M, Rampe D: Discovery of a small molecule activator of the human ether-a-go-go-related gene (HERG) cardiac K+ channel. Mol Pharmacol. 2005 Mar;67(3):827-36. Epub 2004 Nov 17. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Potassium ion leak channel activity
- Specific Function
- Ion channel that contributes to passive transmembrane potassium transport (PubMed:23169818). Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward...
- Gene Name
- KCNK2
- Uniprot ID
- O95069
- Uniprot Name
- Potassium channel subfamily K member 2
- Molecular Weight
- 47092.215 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Roukoz H, Saliba W: Dofetilide: a new class III antiarrhythmic agent. Expert Rev Cardiovasc Ther. 2007 Jan;5(1):9-19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Inward rectifier potassium channel activity
- Specific Function
- Inward rectifying potassium channel that is activated by phosphatidylinositol 4,5-bisphosphate and that probably participates in controlling the resting membrane potential in electrically excitable...
- Gene Name
- KCNJ12
- Uniprot ID
- Q14500
- Uniprot Name
- ATP-sensitive inward rectifier potassium channel 12
- Molecular Weight
- 49000.6 Da
References
- Kiehn J, Wible B, Lacerda AE, Brown AM: Mapping the block of a cloned human inward rectifier potassium channel by dofetilide. Mol Pharmacol. 1996 Aug;50(2):380-7. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Walker DK, Alabaster CT, Congrave GS, Hargreaves MB, Hyland R, Jones BC, Reed LJ, Smith DA: Significance of metabolism in the disposition and action of the antidysrhythmic drug, dofetilide. In vitro studies and correlation with in vivo data. Drug Metab Dispos. 1996 Apr;24(4):447-55. [Article]
- Yamreudeewong W, DeBisschop M, Martin LG, Lower DL: Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Saf. 2003;26(6):421-38. doi: 10.2165/00002018-200326060-00004. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- Safety Data Sheet, Netupitant [Link]
Drug created at June 13, 2005 13:24 / Updated at January 03, 2023 04:16