What is the use of Dofetilide (anti-arrhythmic medication)?

From the Guidelines

Dofetilide should be used with caution and under close monitoring due to its potential to cause QT prolongation and torsades de pointes, and its initiation should be in a hospital setting with careful dose titration based on renal function and QT interval, as supported by the 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation 1.

Key Considerations for Dofetilide Use

• Dofetilide is a Class III antiarrhythmic medication used to treat atrial fibrillation and atrial flutter by blocking potassium channels in the heart, prolonging the cardiac action potential, and increasing the refractory period to restore and maintain normal sinus rhythm.
• The typical dosing ranges from 125 to 500 mcg twice daily, with the specific dose determined by the patient's creatinine clearance and QTc interval, as outlined in the acc/aha/esc guidelines for the management of patients with atrial fibrillation 1.
• Initiation of dofetilide in a hospital setting with continuous cardiac monitoring for at least 3 days is crucial due to the risk of torsades de pointes, with most incidents occurring within the first 3 days of treatment, as noted in the SAFIRE-D and EMERALD studies 1.
• Regular ECG monitoring and kidney function tests are necessary during treatment to minimize the risk of adverse effects.
• Dofetilide is contraindicated in patients with severe renal impairment, prolonged QT intervals, or those taking medications that interact with it, such as verapamil, ketoconazole, or trimethoprim, as highlighted in the guidelines for the management of patients with atrial fibrillation 1.

Monitoring and Patient Education

• Patients should be advised to report any symptoms of arrhythmia like dizziness, palpitations, or fainting immediately.
• The medication should only be prescribed by healthcare providers who have completed a specialized education program due to its significant risks, emphasizing the need for careful patient selection and monitoring.
• The incidence of torsades de pointes with dofetilide treatment is a significant concern, with a reported incidence of 0.8% in the SAFIRE-D study, underscoring the importance of close monitoring and appropriate dose adjustment 1.

From the FDA Drug Label

TIKOSYN (dofetilide) can cause serious ventricular arrhythmias, primarily Torsade de Pointes (TdP) type ventricular tachycardia, a polymorphic ventricular tachycardia associated with QT interval prolongation. 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 The overall incidence of Torsade de Pointes was 0.8%. The frequency of TdP by dose is shown in Table 4.

The main risk of Dofetilide is Torsade de Pointes (TdP), a type of ventricular tachycardia associated with QT interval prolongation.

• The incidence of TdP is 0.8% in patients with supraventricular arrhythmias.
• Dose adjustment according to creatinine clearance and ECG monitoring can reduce the risk of TdP.
• The majority of TdP episodes occur within the first three days of Dofetilide therapy 2.

From the Research

Dofetilide Overview

• Dofetilide is a class III antiarrhythmic agent approved for the conversion of atrial fibrillation and atrial flutter and maintenance of sinus rhythm in symptomatic patients with persistent arrhythmia 3, 4.
• It works by selectively blocking the rapid component of the delayed rectifier outward potassium current (I(kr)), prolonging the effective refractory period and increasing the likelihood of a re-entrant wavefront encountering refractory tissue and terminating the arrhythmia 3, 5.

Efficacy and Safety

• Clinical trials have shown dofetilide to be effective in converting atrial fibrillation and atrial flutter to sinus rhythm, with a higher conversion rate compared to other antiarrhythmic agents such as flecainide and sotalol 3, 5.
• Dofetilide has an acceptable safety profile when initiated under hospital monitoring and dosed according to creatinine clearance, with a risk of torsade de pointes ventricular tachycardia that is dose-dependent and can be minimized with proper precautions 3, 4, 6.
• Common side effects include headache, chest pain, and dizziness, while torsade de pointes is the most serious side effect, occurring in 0.3-10.5% of patients 3, 5.

Clinical Use

• Dofetilide is generally well tolerated and a good choice for patients with acceptable renal function and a normal QT interval, especially if atrioventricular nodal blockade needs to be avoided 4.
• It has been used off-label with success in patients with paroxysmal atrial fibrillation and atrial flutter, as well as atrial tachycardia and ventricular tachycardia 4.
• The therapeutic blood level range of dofetilide is presently unknown, and monitoring of dofetilide blood levels is not available at this time 3.