Dofetilide is a pure class III antiarrhythmic that selectively blocks the rapid component of the delayed rectifier potassium current (IKr). It is used for conversion and maintenance of sinus rhythm in atrial fibrillation/flutter. Due to its QT-prolonging properties and risk of torsades de pointes, initiation requires 3 days of in-hospital ECG monitoring. It is only available through the Tikosyn Education Program (T.I.P.S.).
Effective for conversion and maintenance of sinus rhythm in AF/AFL7
No negative inotropic effects (safe in heart failure)1,2
Pure class III mechanism (no mixed pharmacology)
No increase in mortality in heart failure patients (DIAMOND-HF)6,1
What to watch for
QT prolongation and torsades de pointes (~3% risk)
Headache
Dizziness
Baseline QTc >440 ms (>500 ms if ventricular conduction abnormality)6
CrCl <20 mL/min
The bottom line
Evidence rating moderate. Most-documented uses: effective for conversion and maintenance of sinus rhythm in af/afl, no negative inotropic effects (safe in heart failure), pure class iii mechanism (no mixed pharmacology). 10 sources indexed (2017–2024), with 2 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Selectively blocks the rapid component of the delayed rectifier potassium current (IKr) without affecting other potassium currents (IKs, IK1) or sodium/calcium channels. Prolongs the effective refractory period in atrial and ventricular tissue. Prolongs QT interval in a dose-dependent and concentration-dependent manner. No significant beta-blocking, alpha-blocking, or negative inotropic activity.
Class
Class III Antiarrhythmic
Dosing
Dosing & protocol.
Common range
125–500 mcg twice daily, adjusted by CrCl and QTc response (as prescribed by your physician)
Recommended form
Oral capsule
Can be taken with or without food; renally eliminated, strict dose adjustment by creatinine clearance is mandatory
Safety
Full safety detail.
Side effects
QT prolongation and torsades de pointes (~3% risk)
Headache
Dizziness
Nausea
Chest pain
Insomnia
Contraindications
Baseline QTc >440 ms (>500 ms if ventricular conduction abnormality)6
CrCl <20 mL/min
Congenital or acquired long QT syndromes
Concurrent use with verapamil, cimetidine, trimethoprim, ketoconazole, prochlorperazine, megestrol, or HCTZ (drug interactions that increase dofetilide levels)
Dofetilide prolongs the QT interval and can cause torsades de pointes, particularly when potassium is low. Maintaining normal serum potassium is a core safety measure during dofetilide initiation and ongoing therapy. Potassium supplements should be treated like a monitored medication because both low and high potassium can be dangerous.
Recommendation: Keep potassium in the normal range and follow your prescriber's lab-monitoring plan, especially during dofetilide initiation, dose changes, illness with vomiting or diarrhea, or diuretic use. Do not start potassium supplements unless your clinician is monitoring your blood level and kidney function.
Dofetilide can cause torsades de pointes, and low magnesium is a recognized risk factor. Maintaining normal magnesium helps reduce susceptibility to early afterdepolarizations and supports potassium repletion. Oral magnesium can help prevent or correct low magnesium, but acute torsades requires emergency management.
Recommendation: Maintain adequate magnesium intake and ask about magnesium checks if you take diuretics, PPIs, or have gastrointestinal losses. Do not use high-dose magnesium without monitoring if you have kidney disease, and seek urgent care for fainting, near-fainting, or new sustained palpitations.
Tagle-Cornell MC, Ayoub C, Bird C et al.. Safety of dofetilide in stable patients and investigating traits of susceptibility to torsade de pointes. International journal of cardiology. Heart & vasculature. 2024
Chen C, Lal M, Burton Y et al.. Efficacy and safety of dofetilide and sotalol in patients with hypertrophic cardiomyopathy. Communications medicine. 2023
Cicirale C, Jackson J, Gothard D. Safety of Inpatient Dofetilide Initiation per Cardiology Services: A Retrospective Review. Journal of pharmacy practice. 2022
Rickard JP, Negrelli J, Olson JL et al.. Frequency of Adverse Event Monitoring in Ambulatory Patients on Amiodarone or Dofetilide. Journal of pharmacy practice. 2018
Cho JH, Youn SJ, Moore JC et al.. Safety of Oral Dofetilide Reloading for Treatment of Atrial Arrhythmias. Circulation. Arrhythmia and electrophysiology. 2017
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