What is the recommended dosing for Tikosyn (dofetilide) loading in a patient with potential Impaired renal function?

From the Guidelines

Tikosyn (dofetilide) dosing in patients with impaired renal function requires careful adjustment based on creatinine clearance (CrCl), with the most recent guidelines recommending the following starting doses: for CrCl >60 mL/min, start with 500 mcg twice daily; for CrCl 40-60 mL/min, start with 250 mcg twice daily; for CrCl 20-39 mL/min, start with 125 mcg twice daily; and Tikosyn is not recommended for patients with CrCl <20 mL/min 1.

Key Considerations

• The dose of Tikosyn should be adjusted based on the patient's renal function, as impaired renal function can increase the risk of QT prolongation and torsades de pointes 1.
• Patients should be hospitalized for a minimum of 3 days with continuous ECG monitoring during the initial loading phase.
• Dose adjustments should be made based on QTc interval measurements, with dose reduction or discontinuation if QTc increases excessively (>500 ms or increases by >15% from baseline) 1.
• Concomitant medications that inhibit renal cation transport or CYP3A4 metabolism should be avoided as they may increase dofetilide levels.

Monitoring and Precautions

• Renal function should be assessed before initiation and periodically during treatment, as dofetilide is primarily eliminated by the kidneys.
• Careful monitoring is essential because impaired renal function increases dofetilide plasma concentrations, which can lead to QT prolongation and potentially life-threatening ventricular arrhythmias like torsades de pointes.
• The European Society of Cardiology recommends avoiding dofetilide if CrCl <20 mL/min and individualizing doses according to the QTc interval, renal function, and serum K+ and Mg2+ 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Therapy with TIKOSYN must be initiated (and, if necessary, re-initiated) in a setting that provides continuous electrocardiographic (ECG) monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. The dose of TIKOSYN must be individualized according to calculated creatinine clearance and QTc. The usual recommended dose of TIKOSYN is 500 mcg BID, as modified by the dosing algorithm described below. Step 3. Starting Dose: The starting dose of TIKOSYN is determined as follows: Calculated Creatinine Clearance TIKOSYN Dose

60 mL/min 500 mcg twice daily 40 – 60 mL/min 250 mcg twice daily 20 – <40 mL/min 125 mcg twice daily <20 mL/min Dofetilide is contraindicated in these patients

The recommended dosing for Tikosyn (dofetilide) loading in a patient with potential impaired renal function is as follows:

• Calculated Creatinine Clearance:

  • 60 mL/min: 500 mcg twice daily

  • 40 – 60 mL/min: 250 mcg twice daily
  • 20 – <40 mL/min: 125 mcg twice daily
  • <20 mL/min: Dofetilide is contraindicated in these patients The dose must be individualized according to calculated creatinine clearance and QTc, and the patient should be continuously monitored by ECG for a minimum of three days 2.

From the Research

Tikosyn Loading Dosing

• The recommended dosing for Tikosyn (dofetilide) loading in patients with potential impaired renal function is not explicitly stated in the provided studies.
• However, it is mentioned that the dose of dofetilide should be adjusted according to creatinine clearance and QT interval 3.
• A study found that patients who received nonstandard initial doses of dofetilide or sotalol had 4.7 times greater odds of experiencing a safety-related event requiring dose reduction or discontinuation 4.
• Another study suggested that higher than recommended initial doses of sotalol or dofetilide were associated with a higher incidence of QTc prolongation and more frequent therapy modification 5.
• It is recommended to start treatment with dofetilide in an inpatient monitored setting for the first 3 days to minimize the risk of torsades de pointes 3.
• The concomitant use of drugs that increase the plasma level of dofetilide, such as cimetidine, ketoconazole, trimethoprim-sulfamethoxazole, and verapamil, is contraindicated 3.

Impaired Renal Function Considerations

• Patients with impaired renal function may require dose adjustments due to the increased risk of QTc prolongation and torsades de pointes 6, 5.
• A study found that the odds of QTc prolongation among inpatients receiving dofetilide or sotalol were increased in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) compared to those without heart failure 6.
• It is essential to monitor patients with impaired renal function closely during the initiation of dofetilide and adjust the dose accordingly to minimize the risk of adverse events 4, 3, 5.