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

From the Guidelines

Dofetilide is a recommended treatment option for patients with atrial fibrillation, particularly those with structural heart disease, due to its efficacy in maintaining sinus rhythm and preventing arrhythmia recurrence, as supported by studies such as the SAFIRE-D and DIAMOND trials 1. The medication works by blocking potassium channels in the heart, which prolongs the cardiac action potential and increases the effective refractory period, helping to restore and maintain normal sinus rhythm. Key considerations for dofetilide use include:

• Typical dosing ranges from 125 to 500 mcg twice daily, with the specific dose determined by the patient's creatinine clearance and QTc interval 1.
• Mandatory hospitalization with continuous cardiac monitoring for at least 3 days is required for initiation of therapy due to the risk of QT prolongation and life-threatening ventricular arrhythmias, particularly torsades de pointes 1.
• Dose adjustments are necessary for patients with renal impairment, and regular ECG monitoring is essential throughout treatment 1.
• Significant drug interactions, particularly with medications that inhibit its metabolism or independently prolong the QT interval, require a thorough medication review before starting therapy 1. Despite these precautions, dofetilide remains an important option for rhythm control in patients with atrial arrhythmias, especially those with structural heart disease where other antiarrhythmics may be contraindicated. Some of the benefits of dofetilide include:
• Efficacy in maintaining sinus rhythm, with 58% efficacy in maintaining sinus rhythm 1 year after cardioversion compared to 25% in the placebo group in the SAFIRE-D study 1.
• Ability to prevent arrhythmia recurrence, with 79% of patients in the DIAMOND study maintaining sinus rhythm compared to 42% in the placebo group 1. However, it is crucial to carefully weigh the benefits and risks of dofetilide, considering the potential for torsades de pointes and other adverse effects, and to closely monitor patients during treatment.

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 by the Food and Drug Administration for the conversion of atrial fibrillation and atrial flutter and maintenance of sinus rhythm in symptomatic patients with persistent arrhythmia 3.
• 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 3.

Efficacy and Safety

• Dofetilide has demonstrated efficacy in the conversion of atrial fibrillation or flutter to sinus rhythm and the maintenance of sinus rhythm 4, 5.
• The real-world acute conversion rate of atrial fibrillation and atrial flutter is higher than that reported in clinical trials 3.
• Dofetilide has an acceptable safety profile when initiated (or reloaded) under hospital monitoring and dosed according to creatinine clearance 3.
• However, dofetilide has proarrhythmic potential, and torsade de pointes ventricular tachycardia has been reported in up to 3.3% of patients who received oral dofetilide in some studies 4, 6.

Comparative Studies

• Dofetilide has been compared to other antiarrhythmic agents, such as amiodarone, in the acute termination of atrial fibrillation and flutter 6.
• Intravenous dofetilide was found to be more effective than amiodarone or placebo in restoring sinus rhythm in patients with atrial fibrillation or flutter 6.
• However, dofetilide was associated with a significant incidence of torsade de pointes when infused intravenously at a certain dose and rate 6.

Patient Selection

• Dofetilide is 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 3.
• Caution must be used when initiating dofetilide therapy to avoid torsade de pointes ventricular tachycardia, especially in patients with heart failure, hypertrophy, bradycardia, and female gender 5.