Tikosyn (Dofetilide) Renal Dosing
Dofetilide dosing must be adjusted based on creatinine clearance calculated using the Cockcroft-Gault equation, with doses ranging from 500 mcg twice daily for normal renal function down to contraindication when creatinine clearance falls below 20 mL/min. 1
Dosing Algorithm Based on Creatinine Clearance
The FDA-approved dosing schedule for dofetilide is strictly determined by calculated creatinine clearance 1:
- CrCl >60 mL/min: 500 mcg twice daily 2, 1
- CrCl 40-60 mL/min: 250 mcg twice daily 2, 1
- CrCl 20-40 mL/min: 125 mcg twice daily 2, 1
- CrCl <20 mL/min: Contraindicated 2, 1
Critical Calculation Requirements
You must use the Cockcroft-Gault equation with actual body weight to calculate creatinine clearance before initiating dofetilide. 1 The specific formulas are 1:
- Males: CrCl = (140 - age) × actual body weight (kg) / [72 × serum creatinine (mg/dL)]
- Females: CrCl = (140 - age) × actual body weight (kg) × 0.85 / [72 × serum creatinine (mg/dL)]
Common Pitfall: Do NOT Use MDRD Equation
Never use the MDRD equation or eGFR for dofetilide dosing calculations. 3 The MDRD equation significantly overestimates creatinine clearance in elderly patients, leading to 2-fold higher initial doses that can cause dangerous QTc prolongation 3. In documented cases, using MDRD resulted in a 32% increase in QTc interval from baseline, requiring dose reduction 3.
Body Weight Considerations in Obese Patients
Use total body weight with caution in women with BMI ≥30, as it may lead to higher rates of dose adjustments compared to ideal body weight. 4 Total body weight for starting doses was associated with 3.69 times greater odds of dose adjustments compared to ideal body weight 4.
Mandatory Monitoring Requirements
Dofetilide carries significant risk of torsade de pointes (0.3-10.5% of patients), which is dose-related 5. The following monitoring is required 1:
- Hospitalization for minimum 3 days with continuous ECG monitoring 1, 5
- QTc measurement at 2-3 hours after each dose for the first 5 doses 1
- Discontinue if QTc >500 msec (550 msec with ventricular conduction abnormalities) 1
- Reduce dose if QTc increases >15% from baseline 1
Renal Function Reassessment
Renal function and QTc must be re-evaluated every 3 months or as medically warranted. 1 If renal function deteriorates, recalculate creatinine clearance and adjust the dose according to the algorithm above 1. Approximately 80% of dofetilide is excreted unchanged in the urine, making renal dosing adjustments critical 5.
Drug Interactions Affecting Renal Elimination
Avoid drugs that interfere with renal elimination of dofetilide, as these can increase plasma concentrations and risk of torsade de pointes 6. The elimination half-life is approximately 10 hours in patients with normal renal function but is prolonged in renal impairment 5.
Electrolyte Requirements
Maintain serum potassium within normal range (generally >3.6-4.0 mEq/L) before and during dofetilide therapy. 1 Hypokalemia must be corrected before initiation to minimize arrhythmia risk 1.