Dofetilide

Dofetilide shows 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, I Kr .

• Maintenance of Normal Sinus Rhythm (Delay in AF/AFl Recurrence) TIKOSYN is indicated 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. Because TIKOSYN can cause life threatening ventricular arrhythmias, it should be reserved for patients in whom atrial fibrillation/atrial flutter is highly symptomatic.ICD-10: I48.91

• TIKOSYN is contraindicated in patients with congenital or acquired long QT syndromes. TIKOSYN should not be used in patients with a baseline QT interval or QTc >440 msec (500 msec in patients with ventricular conduction abnormalities).contraindicated

• Therapy with TIKOSYN must be initiated (and, if necessary, re-initiated) in a setting that provides continuous electrocardiographic (ECG) monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Patients should continue to be monitored in this way for a minimum of three days. Additionally, patients should not be discharged within 12 hours of electrical or pharmacological conversion to normal sinus rhythm. • The dose of TIKOSYN must be individualized according to calculated creatinine clearance and QTc. (QT interval should be used if the heart rate is <60 beats per minute. There are no data on use of TIKOSYN when the heart rate is <50 beats per minute.) The usual recommended dose of TIKOSYN is 500 mcg BID, as modified by the dosing algorithm described below. For consideration of a lower dose, see Special Considerations below. • Serum potassium should be maintained within the normal range before TIKOSYN treatment is initiated and should be maintained within the normal range while the patient remains on TIKOSYN therapy. (See WARNINGS, Hypokalemia and Potassium-Depleting Diuretics ). In clinical trials, potassium levels were generally maintained above 3.6–4.0 mEq/L. • Patients with atrial fibrillation should be anticoagulated according to usual medical practice prior to electrical or pharmacological cardioversion. Anticoagulant therapy may be continued after cardioversion according to usual medical practice for the treatment of people with AF.

Ventricular Arrhythmia: TIKOSYN (dofetilide) can cause serious ventricular arrhythmias, primarily Torsade de Pointes (TdP) type ventricular tachycardia, a polymorphic ventricular tachycardia associated with QT interval prolongation. QT interval prolongation is directly related to dofetilide plasma concentration. Factors such as reduced creatinine clearance or certain dofetilide drug interactions will increase dofetilide plasma concentration. The risk of TdP can be reduced by controlling the plasma concentration through adjustment of the initial dofetilide dose according to creatinine clearance and by monitoring the ECG for excessive increases in the QT interval. Treatment with dofetilide must therefore be started only in patients placed for a minimum of three days in a facility that can provide electrocardiographic monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Calculation of the creatinine clearance for all patients must precede administration of the first dose of dofetilide. For detailed instructions regarding dose selection, see DOSAGE AND ADMINISTRATION . The risk of dofetilide induced ventricular arrhythmia was assessed in three ways in clinical studies: 1) by description of the QT interval and its relation to the dose and plasma concentration of dofetilide; 2) by observing the frequency of TdP in TIKOSYN-treated patients according to dose; 3) by observing the overall mortality rate in patients with atrial fibrillation and in patients with structural heart disease.

The TIKOSYN clinical program involved approximately 8,600 patients in 130 clinical studies of normal volunteers and patients with supraventricular and ventricular arrhythmias. TIKOSYN was administered to 5,194 patients, including two large, placebo-controlled mortality trials (DIAMOND CHF and DIAMOND MI) in which 1,511 patients received TIKOSYN for up to three years. In the following section, adverse reaction data for cardiac arrhythmias and non-cardiac adverse reactions are presented separately for patients included in the supraventricular arrhythmia development program and for patients included in the DIAMOND CHF and MI mortality trials (see CLINICAL STUDIES, Safety in Patients with Structural Heart Disease, DIAMOND Studies , for a description of these trials). In studies of patients with supraventricular arrhythmias, a total of 1,346 and 677 patients were exposed to TIKOSYN and placebo for 551 and 207 patient years, respectively. A total of 8.7% of patients in the dofetilide groups were discontinued from clinical trials due to adverse events compared to 8.0% in the placebo groups. The most frequent reason for discontinuation (>1%) was ventricular tachycardia (2.0% on dofetilide vs. 1.3% on placebo). The most frequent adverse events were headache, chest pain, and dizziness. Serious Arrhythmias and Conduction Disturbances: Torsade de Pointes is the only arrhythmia that showed a dose-response relationship to TIKOSYN treatment. It did not occur in placebo treated patients.

Pregnancy Dofetilide has been shown to adversely affect in utero growth and survival of rats and mice when orally administered during organogenesis at doses of 2 or more mg/kg/day. Other than an increased incidence of non-ossified 5 th metacarpal, and the occurrence of hydroureter and hydronephroses at doses as low as 1 mg/kg/day in the rat, structural anomalies associated with drug treatment were not observed in either species at doses below 2 mg/kg/day. The clearest drug-effect associations were for sternebral and vertebral anomalies in both species; cleft palate, adactyly, levocardia, dilation of cerebral ventricles, hydroureter, hydronephroses, and unossified metacarpal in the rat; and increased incidence of unossified calcaneum in the mouse. The "no observed adverse effect dose" in both species was 0.5 mg/kg/day. The mean dofetilide AUCs (0–24hr) at this dose in the rat and mouse are estimated to be about equal to the maximum likely human AUC and about half the likely human AUC, respectively. There are no adequate and well controlled studies in pregnant women. Therefore, dofetilide should only be administered to pregnant women where the benefit to the patient justifies the potential risk to the fetus.

Metabolism

Pharmacokinetics, General Absorption and Distribution: The oral bioavailability of dofetilide is >90%, with maximal plasma concentrations occurring at about 2–3 hours in the fasted state. Oral bioavailability is unaffected by food or antacid.

There is no known antidote to TIKOSYN; treatment of overdose should therefore be symptomatic and supportive. The most prominent manifestation of overdosage is likely to be excessive prolongation of the QT interval. In cases of overdose, cardiac monitoring should be initiated. Charcoal slurry may be given soon after overdosing but has been useful only when given within 15 minutes of TIKOSYN administration. Treatment of Torsade de Pointes or overdose may include administration of isoproterenol infusion, with or without cardiac pacing. Administration of intravenous magnesium sulfate may be effective in the management of Torsade de Pointes. Close medical monitoring and supervision should continue until the QT interval returns to normal levels. Isoproterenol infusion into anesthetized dogs with cardiac pacing rapidly attenuates the dofetilide-induced prolongation of atrial and ventricular effective refractory periods in a dose-dependent manner. Magnesium sulfate, administered prophylactically either intravenously or orally in a dog model, was effective in the prevention of dofetilide-induced Torsade de Pointes ventricular tachycardia.

• Oct 1, 1999NDANDA020931Pfizer
• Jun 6, 2016ANDAANDA207058Dr Reddys Labs Sa
• Mar 26, 2018ANDAANDA207746Sigmapharm Labs Llc
• Apr 10, 2018ANDAANDA208625Bionpharma
• Oct 9, 2018ANDAANDA210466Sun Pharm
• Jan 22, 2019ANDAANDA210740Aurobindo Pharma Ltd
• Jan 29, 2020ANDAANDA213220Msn
• Jun 19, 2020ANDAANDA213338Accord Hlthcare

1. 1Atrial Fibrillation1,06010%
2. 2Drug Ineffective1,0269.9%
3. 3Dyspnoea6075.8%
4. 4Dizziness5565.4%
5. 5Fatigue5275.1%
6. 6Death4844.7%
7. 7Electrocardiogram Qt Prolonged4454.3%
8. 8Headache3913.8%
9. 9Malaise3223.1%
10. 10Diarrhoea3193.1%
11. 11Drug Interaction2982.9%
12. 12Nausea2912.8%
13. 13Asthenia2872.8%
14. 14Heart Rate Increased2862.8%
15. 15Arrhythmia2652.6%

The 10 most recently updated of 22 ClinicalTrials.gov registrations naming Dofetilide as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Using an iPhone ECG to Monitor the QT Interval on Dofetilide and Sotalol Patients
  Completed · Interventional · 29 enrolled · University of Oklahoma
  NCT02241252updated 2026-04-07
• Pulsed Field Ablation (PFA) vs Anti-Arrhythmic Drug (AAD) Therapy as a First Line Treatment for Persistent Atrial Fibrillation
  Active not recruiting · Interventional · 484 enrolled · Boston Scientific Corporation
  NCT06096337updated 2026-03-31
• The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
  Recruiting · Phase 4 · Interventional · 100 enrolled · University of Rochester
  NCT05034432updated 2026-03-23
• Assessing the Neurological Outcomes After Atrial Fibrillation Ablation for Rhythm Control
  Not yet recruiting · Observational · 100 enrolled · Kansas City Heart Rhythm Research Foundation
  NCT06783868updated 2025-08-28
• Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
  Terminated · Phase 1 · Phase 2 · Interventional · 42 enrolled · Thryv Therapeutics, Inc.
  NCT05906732updated 2025-07-24
• A Comparison of Antiarrhythmic Drug Therapy and Radio Frequency Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation
  Completed · Phase 4 · Interventional · 112 enrolled · Biosense Webster, Inc.
  NCT00540787updated 2025-02-28
• First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Persistent Atrial Fibrillation Treatment (RAAFT-3)
  Completed · Phase 3 · Interventional · 25 enrolled · University of Pennsylvania
  NCT04037397updated 2024-11-12
• Genetics of QT Prolongation With Antiarrhythmics
  Unknown · Observational · 1,000 enrolled · Massachusetts General Hospital
  NCT02439658updated 2022-04-04
• Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial
  Completed · Interventional · 2,204 enrolled · Mayo Clinic
  NCT00911508updated 2021-04-21
• Improvement in Endothelial Dysfunction After Initiation of Anti-arrhythmic Therapy in Atrial Fibrillation Patients
  Completed · Observational · 12 enrolled · Samir Saba
  NCT04128878updated 2021-01-14

Frequently asked questions

How does Dofetilide work?

Dofetilide shows 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, I Kr .

What is Dofetilide used for?

According to FDA labeling, Dofetilide carries indications including: Maintenance of Normal Sinus Rhythm (Delay in AF/AFl Recurrence) TIKOSYN is indicated 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. Because TIKOSYN can cause life threatening ventricular arrhythmias, it should be reserved for patients in whom atrial fibrillation/atrial flutter is highly symptomatic.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Dofetilide?

Dofetilide is classified as Antiarrhythmics, class III, Antiarrhythmic, Potassium Channel Interactions.

What are the brand names for Dofetilide?

Dofetilide is marketed under brand names including Tikosyn.

What are the contraindications for Dofetilide?

Dofetilide labeling lists contraindications including: TIKOSYN is contraindicated in patients with congenital or acquired long QT syndromes. TIKOSYN should not be used in patients with a baseline QT interval or QTc >440 msec (500 msec in patients with ventricular conduction abnormalities).. Always consult the full prescribing information and a clinician.