cardio:arrhythmias:dofetilide []

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====== Dofetilide ======

Dofetilide is a pure Class III antiarrhythmic that blocks cardiac potassium channels.

It prolongs repolarization and increases refractory period without significant sodium, beta, or calcium channel effects.

→ [[cardio:arrhythmias:start|Dysrhythmias Module]]

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===== Mechanism of Action =====

• Selectively blocks IKr (rapid delayed rectifier potassium current)
• Prolongs Phase 3 repolarization
• Prolongs QT interval
• Increases action potential duration

Net Effect:

• Suppresses atrial arrhythmias
• Maintains sinus rhythm

Unlike [[cardio:arrhythmias:amiodarone|Amiodarone]], dofetilide has no multi-class effects.

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===== Indications =====

==== Atrial Fibrillation / Atrial Flutter ====

• Rhythm control
• Maintenance of sinus rhythm

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==== Heart Failure with Atrial Fibrillation ====

• Safe in HFrEF
• One of few rhythm agents allowed in systolic heart failure

→ [[cardio:heart_failure:start|Heart Failure Module]]

Dofetilide is NOT used for ventricular arrhythmias.

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===== Major Risk: Torsades de Pointes =====

Dofetilide significantly prolongs QT interval.

Risk factors:

• Renal impairment
• Hypokalemia
• Hypomagnesemia
• Concomitant QT-prolonging drugs

QT prolongation is dose-dependent.

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===== Mandatory Hospital Initiation =====

Dofetilide must be initiated inpatient.

Requirements:

• Baseline ECG
• Continuous telemetry
• Serial QT measurements
• Renal function assessment
• Dose adjustment based on creatinine clearance

This requirement is exam-critical.

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===== Pharmacokinetics =====

• Renally cleared
• Requires dose adjustment in CKD
• Minimal hepatic metabolism

Renal dosing is essential to reduce torsades risk.

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===== Contraindications =====

• Baseline prolonged QT
• Severe renal impairment
• Concomitant QT-prolonging drugs
• Electrolyte abnormalities

Avoid with strong CYP3A4 inhibitors.

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===== Dofetilide vs Other Class III Agents =====

[[cardio:arrhythmias:amiodarone|Amiodarone]]:
• Most effective
• Multi-system toxicity
• Lower torsades risk

[[cardio:beta_blockers:sotalol|Sotalol]]:
• Beta-blocker + Class III
• Also prolongs QT
• Renally cleared

Dofetilide:
• Pure Class III
• Higher torsades risk
• Requires inpatient initiation
• Safe in HFrEF

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===== Clinical Pearls =====

✔ Pure potassium channel blocker  
✔ Prolongs QT significantly  
✔ High torsades risk  
✔ MUST be started in hospital  
✔ Safe rhythm-control agent in HFrEF  

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Related:

→ [[cardio:arrhythmias:start|Dysrhythmias Module]]
→ [[cardio:arrhythmias:amiodarone|Amiodarone]]
→ [[cardio:beta_blockers:sotalol|Sotalol]]
→ [[cardio:heart_failure:start|Heart Failure Module]]
→ [[cardio:intro:start|Return to Cardiovascular Modules]]