What are the monitoring requirements for dofetilide (antiarrhythmic medication) therapy?

Dofetilide Monitoring Requirements

Dofetilide therapy requires mandatory hospitalization for initiation or reinitiation with continuous electrocardiographic monitoring for a minimum of three days and should not be started in patients with QTc >440 msec (500 msec in patients with ventricular conduction abnormalities). 1

Initial Hospitalization Requirements

Baseline Assessment

• ECG monitoring: Obtain baseline QTc using average of 5-10 beats
• Laboratory testing:
  • Serum potassium and magnesium (must be within normal range)
  • Serum creatinine for calculation of creatinine clearance
• Contraindications: Do not initiate if QTc >440 msec (500 msec with ventricular conduction abnormalities) or CrCl <20 mL/min 1

Dosing Protocol

1. Calculate creatinine clearance using appropriate formula
2. Determine starting dose based on renal function:
   • CrCl >60 mL/min: 500 mcg twice daily
   • CrCl 40-60 mL/min: 250 mcg twice daily
   • CrCl 20-<40 mL/min: 125 mcg twice daily
   • CrCl <20 mL/min: Contraindicated 1

Monitoring During Hospitalization

• Continuous ECG monitoring for minimum 3 days
• QTc assessment at 2-3 hours after each dose
• Dose adjustment if QTc increases >15% from baseline or exceeds 500 msec (550 msec with ventricular conduction abnormalities)
• Discontinuation if QTc exceeds 500 msec (550 msec with ventricular conduction abnormalities) after the second dose 1

Discharge Requirements

• Minimum 3 days of monitoring completed
• QTc within acceptable range
• Patient must have adequate supply of dofetilide at individualized dose until prescription can be filled 1

Outpatient Monitoring

Follow-up Testing

• 12-lead ECG: Every 3-6 months
• More frequent monitoring for patients:
  • Taking other QT-prolonging drugs
  • With changing kidney function
• Laboratory testing at each follow-up:
  • Serum potassium and magnesium
  • Serum creatinine for estimation of creatinine clearance 2

Special Considerations

Reinitiation Protocol

• Mandatory hospitalization for dofetilide reinitiation, even at previously tolerated doses
• Continuous ECG monitoring for minimum 3 days
• Dose adjustments are common (29.4-36.7% of patients) even when reloading at previously tolerated doses 3

Cardioversion Considerations

• If patients do not convert to normal sinus rhythm within 24 hours of dofetilide initiation, electrical cardioversion should be considered
• After successful electrical cardioversion, continue ECG monitoring for 12 hours post-cardioversion or a minimum of 3 days after dofetilide initiation (whichever is greater) 1

Risk of Torsades de Pointes (TdP)

• Risk is directly related to dofetilide plasma concentration
• Overall incidence is 0.8% in supraventricular arrhythmia patients
• Most TdP episodes (10/11 events) occur within first three days of therapy 1
• Risk factors for TdP include:
  • Higher doses
  • Renal dysfunction
  • Electrolyte abnormalities (especially hypokalemia)
  • Concomitant QT-prolonging medications
  • Female sex 4, 5

Common Pitfalls to Avoid

• Failure to calculate creatinine clearance before first dose
• Inadequate ECG monitoring during initiation or dose changes
• Electrolyte imbalances: Ensure potassium and magnesium are normal before and during therapy
• Drug interactions: Avoid concomitant use of medications that interfere with dofetilide metabolism or renal elimination
• Skipping hospitalization for reloading: Even reloading at previously tolerated doses requires hospitalization due to high rate (29.4%) of needed dose adjustments 3
• Assuming normal QT interval means no risk: Proarrhythmia can occur with exercise or other activities even when in-hospital monitoring showed no issues 6

Dofetilide's narrow therapeutic window and significant risk of TdP necessitate strict adherence to these monitoring protocols to ensure patient safety while maximizing therapeutic benefit.