Dofetilide

Dofetilide
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

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Black Box Warning

{{{blackBoxWarningTitle}}} See full prescribing information for complete Boxed Warning. To minimize the risk of induced arrhythmia, patients initiated or re-initiated on TIKOSYN should be placed for a minimum of 3 days in a facility that can provide calculations of creatinine clearance, continuous electrocardiographic monitoring, and cardiac resuscitation. For detailed instructions regarding dose selection, see DOSAGE AND ADMINISTRATION. TIKOSYN is available only to hospitals and prescribers who have received appropriate TIKOSYN dosing and treatment initiation education; see DOSAGE AND ADMINISTRATION.

Overview

Dofetilide is {{{aOrAn}}} Antiarrhythmic that is FDA approved for the {{{indicationType}}} of Maintenance of Normal Sinus Rhythm (Delay in AF/AFl Recurrence), Conversion of Atrial Fibrillation/Flutter. There is a Black Box Warning for this drug as shown here. Common adverse reactions include chest pain, dizziness , headache.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

<h4>Condition 1</h4>

• Dosing Information

(Dosage)

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Dofetilide FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Contraindications

There is limited information regarding Dofetilide Contraindications in the drug label.

Warnings

{{{blackBoxWarningTitle}}} See full prescribing information for complete Boxed Warning. To minimize the risk of induced arrhythmia, patients initiated or re-initiated on TIKOSYN should be placed for a minimum of 3 days in a facility that can provide calculations of creatinine clearance, continuous electrocardiographic monitoring, and cardiac resuscitation. For detailed instructions regarding dose selection, see DOSAGE AND ADMINISTRATION. TIKOSYN is available only to hospitals and prescribers who have received appropriate TIKOSYN dosing and treatment initiation education; see DOSAGE AND ADMINISTRATION.

There is limited information regarding Dofetilide Warnings' in the drug label.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Dofetilide Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Dofetilide Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Dofetilide Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Dofetilide in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dofetilide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Dofetilide during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Dofetilide in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Dofetilide in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Dofetilide in geriatric settings.

Gender

There is no FDA guidance on the use of Dofetilide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Dofetilide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Dofetilide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Dofetilide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Dofetilide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Dofetilide in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Dofetilide Administration in the drug label.

Monitoring

There is limited information regarding Dofetilide Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Dofetilide and IV administrations.

Overdosage

There is limited information regarding Dofetilide overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Dofetilide Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Dofetilide Mechanism of Action in the drug label.

Structure

There is limited information regarding Dofetilide Structure in the drug label.

Pharmacodynamics

There is limited information regarding Dofetilide Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Dofetilide Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Dofetilide Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Dofetilide Clinical Studies in the drug label.

How Supplied

There is limited information regarding Dofetilide How Supplied in the drug label.

Storage

There is limited information regarding Dofetilide Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Dofetilide Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Dofetilide interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Dofetilide Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Dofetilide Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Dofetilide

Clinical data
ATC code	C01BD04 (WHO)
Pharmacokinetic data
Bioavailability	96% (oral)
Protein binding	60% -70%
Elimination half-life	10 hours
Identifiers
IUPAC name N-[4-[2-[2-[4-(methanesulfonamido)phenoxy]ethyl-methyl-amino] ethyl]phenyl] methanesulfonamide
CAS Number	115256-11-6
PubChem CID	71329
DrugBank	APRD00367
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C19H27N3O5S2
Molar mass	441.567 g/mol

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]

For patient information, click here

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.

The chemical name for dofetilide is N-[4-(2-{2-[4-(methanesulphonamido) phenoxyl]-N-methylethylamino}ethyl)phenyl]- methanesulphonamide. It is marketed under the trade name Tikosyn^® by Pfizer, and is available in the United States in capsules containing 125, 250, and 500 µg of dofetilide. Due to the pro-arrhythmic potential of dofetilide, it is only available by prescription by physicians who have undergone specific training in the risks of treatment with dofetilide. In addition, it is only available by mail order or through specially trained local pharmacies to individuals who are prescribed dofetilide by a physician who is registered as being able to prescribe the pharmaceutical.

The elimination half-life of dofetilide is roughly 10 hours, however this is variable based on many physiologic factors (most significantly creatinine clearance), and ranges from 4.8 to 13.5 hours.

Mechanism of action

Dofetilide works by selectively blocking the rapid component of the delayed rectifier outward potassium current (I_Kr).

This causes prolongation of the effective refractory period of accessory pathways (both anterograde and retrograde conduction in the accessory pathway). It is this selective action on accessory pathways that makes dofetilide effective in the treatment of atrial fibrillation and flutter.

Dofetilide does not effect V_max (The slope of the upstroke of phase 0 depolarization), conduction velocity, or the resting membrane potential.

There is a dose-dependent increase in the QT interval and the corrected QT interval (QTc). Because of this, many practitioners will initiate dofetilide therapy only on individuals under telemetry monitoring or if serial EKG measurements of QT and QTc can be performed.

Metabolism

A steady-state plasma level of dofetilide is achieved in 2-3 days.

80% of dofetilide is excreted by the kidneys, so the dose of dofetilide should be adjusted in individuals with renal insufficiency, based on creatinine clearance.

In the kidneys, dofetilide is eliminated via cation exchange (secretion). Agents that interfere with the renal cation exchange system, such as verapamil, cimetidine, hydrochlorothiazide, itraconazole, ketoconazole, prochlorperazine, and trimethoprim should not be administered to individuals taking dofetilide.

About 20 percent of dofetilide is metabolized in the liver via the CYP3A4 isoenzyme of the cytochrome P450 enzyme system. Drugs that interfere with the activity of the CYP3A4 isoenzyme can increase serum dofetilide levels. If the renal cation exchange system is interfered with (as with the medications listed above), a larger percentage of dofetilide is cleared via the CYP3A4 isoenzyme system.

Side effects

Torsades de pointes is the most serious side effect of dofetilide therapy. The incidence of torsades de pointes is dose-related, and is 0.3-10.5%. The risk appears to be dose-dependent, with an increased incidence of torsades de pointes associated with higher doses of dofetilide administered.

The risk of inducing torsades de pointes can be decreased by taking precautions when initiating therapy, such as hospitalizing individuals for a minimum of three days for serial creatinine measurement, continuous telemetry monitoring and availability of cardiac resuscitation.

Clinical use

Based on the results of the Danish Investigations of Arrhythmias and Mortality on Dofetilide (DIAMOND) study, dofetilide does not affect mortality in the treatment of patients post-myocardial infarction with left ventricular dysfunction.³ Because of the results of the DIAMOND study, many physicians use dofetilide in the suppression of atrial fibrillation in individuals with LV dysfunction.

See also

• Antiarrhythmic agents
• Cardiac action potential
• Electrocardiogram

References

1. Thomas L. Lenz, Pharm.D., and Daniel E. Hilleman, Pharm.D., Department of Cardiology, Creighton University, Omaha, Nebraska. Dofetilide, a New Class III Antiarrhythmic Agent. Pharmacotherapy 20(7):776-786, 2000. (Medline abstract)
2. 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. (Medline abstract)
3. 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. (Medline abstract)

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