====== 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]] -------------------------------------------------------------------- ===== 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. -------------------------------------------------------------------- ===== Indications ===== ==== Atrial Fibrillation / Atrial Flutter ==== • Rhythm control • Maintenance of sinus rhythm ---- ==== 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. -------------------------------------------------------------------- ===== 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. -------------------------------------------------------------------- ===== 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. -------------------------------------------------------------------- ===== Pharmacokinetics ===== • Renally cleared • Requires dose adjustment in CKD • Minimal hepatic metabolism Renal dosing is essential to reduce torsades risk. -------------------------------------------------------------------- ===== Contraindications ===== • Baseline prolonged QT • Severe renal impairment • Concomitant QT-prolonging drugs • Electrolyte abnormalities Avoid with strong CYP3A4 inhibitors. -------------------------------------------------------------------- ===== 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 -------------------------------------------------------------------- ===== Clinical Pearls ===== ✔ Pure potassium channel blocker ✔ Prolongs QT significantly ✔ High torsades risk ✔ MUST be started in hospital ✔ Safe rhythm-control agent in HFrEF -------------------------------------------------------------------- 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]]