Dofetilide Topic Review

Dofetilide is a class III antiarrhythmic drug that is used for maintenance of sinus rhythm in patients with atrial fibrillation.

Dofetilide blocks potassium channels in phase 3 of the action potential and slows the efflux of potassium cation back out of the myocyte. This slows the cell repolarization rate and widens the action potential’s plateau phase. [Ibrahim MA, et al. StatPearls [Internet]. 2023;1a]

Dofetilide also prolongs the QT interval, possibly from inhibiting phosphoinositide 3–kinase, which increases the late sodium current. [Ibrahim MA, et al. StatPearls [Internet]. 2023;1a] The incidence of torsades de pointes associated with dofetilide has been reported to be 0.9% to 3.3%. [Joglar JA, et al. J Am Coll Cardiol. 2023;91b]

Dofetilide is “not practical” for acute cardioversion because it takes several days for efficacy, according to the 2023 American College of Cardiology/American Heart Association/American College of Clinical Pharmacy/Heart Rhythm Society Guideline for the Diagnosis and Management of Atrial Fibrillation (AF). [Joglar JA, et al. J Am Coll Cardiol. 2023;82a-b]

Dofetilide is renally excreted and should not be co-administered with cimetidine, dolutegravir, hydrochlorothiazide, hydrochlorothiazide/triamterene, ketoconazole, megestrol, prochlorperazine, trimethoprim, trimethoprim/sulfamethoxazole or verapamil. [Joglar JA, et al. J Am Coll Cardiol. 2023;88h]

Use of dofetilide is reasonable (Class 2a recommendation) for long-term maintenance of sinus rhythm in patients with AF and heart failure with reduced ejection fraction (≤ 40%) and in patients with AF and without significant baseline QT interval prolongation or uncorrected hypokalemia or hypomagnesemia; in the latter population, dose selection should be based on kidney function, and the QT interval, kidney function and serum potassium and magnesium concentrations should be monitored. [Joglar JA, et al. J Am Coll Cardiol. 2023;85a]

Due to potential for proarrhythmia, patients initiating, increasing the dose of or reinitiating dofetilide should be (Class 1 recommendation) admitted for at least 3 days to a facility that can administer ECGs, calculate creatinine clearance and perform cardiac resuscitation. [Joglar JA, et al. J Am Coll Cardiol. 2023;89a]

References:

• Ibrahim MA, et al. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK459154. Updated May 8, 2023. Accessed May 1, 2024.

• Joglar JA, et al. J Am Coll Cardiol. 2023;doi:10.1016/j.jacc.2023.08.017.