What is the role of Tikosyn (Dofetilide) in atrial fibrillation (afib)?

From the Guidelines

Tikosyn (dofetilide) can be used to treat atrial fibrillation (AFib), but requires careful consideration and monitoring due to its significant risks, including torsades de pointes, a life-threatening ventricular arrhythmia, as supported by the most recent guidelines 1.

Key Considerations

• The usual starting dose is 500 mcg twice daily, but this must be adjusted based on kidney function and QT interval, with dose reductions for patients with creatinine clearance 40-60 mL/min to 250 mcg twice daily, and for those with clearance 20-40 mL/min to 125 mcg twice daily, as recommended by previous studies 1.
• Tikosyn works by blocking potassium channels in the heart, which helps restore normal rhythm, and has been shown to be effective in maintaining sinus rhythm in patients with AFib, with a response rate of 58% at 1 year after cardioversion compared to 25% with placebo, as demonstrated in the SAFIRE-D study 1.
• Before starting Tikosyn, patients must discontinue other antiarrhythmic medications for at least five half-lives, and certain medications that interact with Tikosyn must be avoided completely, to minimize the risk of proarrhythmic effects, as highlighted in the guidelines 1.
• Regular ECG monitoring and kidney function tests are essential during treatment, with inpatient monitoring required for at least 3 days during initiation due to the risk of QT prolongation and ventricular arrhythmias, as mandated by the US Food and Drug Administration, and supported by recent updates to practice standards for electrocardiographic monitoring in hospital settings 1.

Important Safety Information

• Tikosyn should only be prescribed by healthcare providers who have completed a specialized education program due to its significant risks, including torsades de pointes, a life-threatening ventricular arrhythmia, as emphasized in the guidelines 1.
• The incidence of torsades de pointes with dofetilide is approximately 0.8%, with most events occurring within the first 3 days of treatment, as reported in the SAFIRE-D study 1.
• Patients should be alerted to the potential significance of symptoms such as syncope, angina pectoris, or dyspnea, and warned about the use of noncardiac drugs that can prolong the QT interval, as recommended in the guidelines 1.

From the FDA Drug Label

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 TIKOSYN is indicated for the conversion of atrial fibrillation and atrial flutter to normal sinus rhythm. TIKOSYN has not been shown to be effective in patients with paroxysmal atrial fibrillation.

The role of Tikosyn (Dofetilide) in atrial fibrillation (afib) is to:

• Maintain normal sinus rhythm: delay the time to recurrence of atrial fibrillation/atrial flutter in patients with afib/atrial flutter of greater than one week duration who have been converted to normal sinus rhythm 2
• Convert afib to normal sinus rhythm: convert atrial fibrillation and atral flutter to normal sinus rhythm 2 Note that Tikosyn has not been shown to be effective in patients with paroxysmal atrial fibrillation 2

From the Research

Role of Tikosyn (Dofetilide) in Atrial Fibrillation (AFib)

• Tikosyn (Dofetilide) is a class III antiarrhythmic agent used for the conversion and maintenance of sinus rhythm in patients with atrial fibrillation (AF) and atrial flutter (AFl) 3, 4, 5.
• It works by selectively blocking the rapid component of the delayed rectifier outward potassium current, prolonging the effective refractory period in accessory pathways, and increasing the likelihood of a re-entrant wavefront encountering refractory tissue and terminating the arrhythmia 3, 4, 5.
• Dofetilide has been shown to be effective in converting AF and AFl to normal sinus rhythm (NSR), with conversion rates ranging from 29% to 70% in clinical trials 3, 5, 6.
• The drug is generally well tolerated, but it can cause torsades de pointes, a potentially life-threatening arrhythmia, in up to 10.5% of patients 3, 7.
• The risk of torsades de pointes can be minimized by adjusting the dosage according to creatinine clearance and QT interval, excluding patients with known risk factors for long QT syndrome and torsades de pointes, and starting treatment in an inpatient monitored setting for the first 3 days 3, 4, 7.
• Dofetilide has been shown to be more effective in maintaining sinus rhythm in patients with atrial flutter (AFl) than in those with atrial fibrillation (AF) 6.
• The long-term use of oral dofetilide in patients at high risk for sudden cardiac death is not associated with an increased risk of mortality 5.

Efficacy and Safety

• Dofetilide has been demonstrated to be effective in terminating persistent AF and AFl, and in maintaining sinus rhythm after direct current cardioversion (CV) 6.
• The efficacy of dofetilide in persistent versus paroxysmal AF/AFl has been compared, with results showing that dofetilide is more effective in patients with persistent AF/AFl than in those with paroxysmal AF/AFl 6.
• Significant proarrhythmia can occur even with careful in-hospital monitoring, highlighting the need for close monitoring and careful dosing of dofetilide 6.

Mechanism and Risk Factors

• The underlying mechanism of dofetilide-induced torsade de pointes (Tdp) involves the blockade of the rapid component of the cardiac delayed rectifier potassium current (I(Kr)), which can lead to QT prolongation and ventricular tachycardia/Tdp 7.
• Risk factors for dofetilide-induced Tdp include renal impairment, QT interval prolongation, and concomitant use of drugs that increase the plasma level of dofetilide 7.
• Precautionary measures to avoid dofetilide-induced QT prolongation and ventricular tachycardia/Tdp include careful dosing, monitoring of QT interval, and exclusion of patients with known risk factors for long QT syndrome and torsades de pointes 7.