Can I start dofetilide in a patient with impaired renal function?

Dofetilide Initiation in a Patient with GFR of 50

Dofetilide can be initiated in a patient with a GFR of 50 mL/min, but requires a reduced starting dose of 250 mcg twice daily with mandatory inpatient monitoring for at least 3 days. 1, 2

Dosing Based on Renal Function

Dofetilide is primarily eliminated by the kidneys (approximately 80% excreted unchanged in urine), making renal function the most critical factor in determining appropriate dosing 2. For patients with a creatinine clearance between 40-60 mL/min, the recommended dosage is:

• Starting dose: 250 mcg twice daily 1, 2
• Dose adjustments based on QTc response during hospitalization

Required Monitoring Protocol

Initiating dofetilide requires strict adherence to the following protocol:

1. Mandatory hospitalization with continuous ECG monitoring for a minimum of 3 days 1

2. Baseline measurements before first dose:

   • QTc interval (average of 5-10 beats)
   • Serum potassium (must be within normal range)
   • Serum magnesium (must be within normal range)
   • Serum creatinine (for accurate GFR calculation) 1

3. QTc monitoring at 2-3 hours after each dose 1

4. Dose adjustment required if:

   • QTc increases >15% from baseline
   • QTc exceeds 500 msec (550 msec with ventricular conduction abnormalities) 1

Safety Considerations

The risk of Torsades de Pointes (TdP) with dofetilide is directly related to plasma concentration, with most episodes occurring within the first three days of therapy 1. Risk factors include:

• Renal dysfunction (already a concern with GFR of 50)
• Electrolyte abnormalities (especially hypokalemia and hypomagnesemia)
• Concomitant QT-prolonging medications
• Female sex 1

Contraindications and Drug Interactions

Several important contraindications and drug interactions must be considered:

• Absolute contraindications:

  • Severe renal impairment (CrCl <20 mL/min) 2
  • QTc >500 ms at baseline 3, 4
  • Concomitant use of:
    • Cimetidine, trimethoprim, prochlorperazine, megestrol, ketoconazole, dolutegravir 2

• Use with caution with other medications that can prolong QT interval 3

Common Pitfalls to Avoid

1. Using incorrect GFR calculation method: Always use Cockcroft-Gault equation for dofetilide dosing, not MDRD or eGFR. Using MDRD can lead to significant dosing errors, particularly in elderly patients 5

2. Inadequate monitoring: Failure to perform continuous ECG monitoring or check QTc after each dose can miss early signs of QT prolongation 1

3. Electrolyte imbalances: Failure to correct potassium and magnesium before initiation increases risk of TdP 1

4. Drug interactions: Not screening for interacting medications that can increase dofetilide levels 2

5. Assuming low risk: Even with normal baseline QT interval, patients can still develop QT prolongation and TdP 1

Long-term Follow-up

After successful initiation:

• Regular 12-lead ECG every 3-6 months
• More frequent monitoring for patients taking other QT-prolonging drugs
• Regular laboratory testing for serum potassium, magnesium, and creatinine 1

In summary, dofetilide can be initiated in a patient with GFR of 50 mL/min at a reduced dose of 250 mcg twice daily, but requires strict adherence to monitoring protocols and careful attention to drug interactions and electrolyte management.