From the Guidelines
Tikosyn (dofetilide) loading dose should be initiated at 500 mcg every 12 hours for patients with creatinine clearance greater than 60 mL/min, with adjustments made based on kidney function and QT interval, as outlined in the most recent guidelines 1. The dosing of Tikosyn (dofetilide) is crucial due to its potential to cause QT prolongation and life-threatening arrhythmias.
- For patients with creatinine clearance 60 mL/min or greater, the initial dose is 500 mcg every 12 hours.
- For patients with creatinine clearance between 40-60 mL/min, the dose should be reduced to 250 mcg every 12 hours.
- For patients with creatinine clearance between 20-40 mL/min, the dose should be further reduced to 125 mcg every 12 hours.
- Tikosyn is contraindicated in patients with creatinine clearance less than 20 mL/min. Key considerations during the initiation of Tikosyn include:
- Continuous cardiac monitoring for a minimum of 3 days due to the risk of QT prolongation and torsades de pointes.
- ECGs should be performed before the first dose, 2-3 hours after each dose, and daily thereafter to monitor for QT interval prolongation.
- Potassium levels should be maintained within the normal range (4.0-5.0 mEq/L) during initiation to minimize the risk of QT prolongation. The mechanism of action of Tikosyn, blocking the rapid component of the delayed rectifier potassium current, is effective in restoring normal sinus rhythm in patients with atrial fibrillation or flutter but necessitates careful monitoring due to its proarrhythmic potential, as highlighted in recent clinical guidelines 1.
From the FDA Drug Label
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 loading dose of Tikosyn (Dofetilide) is not explicitly mentioned in the provided drug label. However, the starting dose is determined based on the calculated creatinine clearance, with possible doses being 500 mcg, 250 mcg, or 125 mcg twice daily.
- The dose is individualized according to calculated creatinine clearance and QTc.
- The usual recommended dose is 500 mcg BID, as modified by the dosing algorithm.
- For consideration of a lower dose, see Special Considerations. 2
From the Research
Dofetilide Loading Dose
- The provided studies do not explicitly state the loading dose of Tikosyn (Dofetilide) 3, 4, 5, 6.
- However, it is mentioned that the initial dosing of dofetilide is based on estimated creatinine clearance (eCrCl) as specified by the drug manufacturer 4.
- One study notes that most patients converted to normal sinus rhythm within 24-36 hours, but it does not provide information on the loading dose 5.
- Another study discusses the importance of proper dosing and monitoring to minimize the risk of torsades de pointes, but it does not specify the loading dose 6.
- A separate study on teicoplanin, an antibiotic drug, discusses loading doses, but this is not relevant to dofetilide 7.
Key Considerations
- Dofetilide dosing must be based on creatinine clearance, and the drug should not be given or discontinued if the QTc is greater than 500 ms 3, 4.
- The use of estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) equation for calculating doses of dofetilide should be avoided 4.