What lab monitoring is required for patients taking Tikosyn (Dofetilide)?

From the Guidelines

Tikosyn (dofetilide) requires careful laboratory monitoring due to its risk of causing QT prolongation and potentially fatal arrhythmias, and patients should have baseline ECG, serum potassium, magnesium, and creatinine measurements before starting therapy, with QTc interval measured at baseline and should be less than 440-450 ms (or <500 ms in patients with ventricular conduction abnormalities) to initiate therapy, as recommended by the 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation 1.

Key Monitoring Requirements

• Baseline ECG, serum potassium, magnesium, and creatinine measurements before starting therapy
• QTc interval measurement at baseline, with a threshold of <440-450 ms (or <500 ms in patients with ventricular conduction abnormalities) to initiate therapy
• Creatinine clearance calculation to determine appropriate dosing, as Tikosyn is primarily eliminated by the kidneys
• Mandatory 3-day hospitalization when starting Tikosyn, with ECGs monitored 2-3 hours after each dose, and additional ECGs if the QTc increases excessively
• Regular monitoring of electrolytes (potassium and magnesium) and maintenance within normal ranges
• ECG monitoring within 3 days after discharge, then periodically (typically every 3-6 months), along with renal function and electrolyte testing

Important Considerations

• Any significant changes in renal function, electrolytes, or concomitant medications require reassessment of Tikosyn dosing and QTc monitoring
• Tikosyn has a narrow therapeutic window, and changes in kidney function or electrolyte imbalances can rapidly increase the risk of life-threatening arrhythmias
• The 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation provides the most recent and highest-quality evidence for the management of patients with atrial fibrillation, including those taking Tikosyn 1

From the FDA Drug Label

At 2–3 hours after administering the first dose of TIKOSYN, determine the QTc If the QTc has increased by greater than 15% compared to the baseline established in Step 1 OR if the QTc is greater than 500 msec (550 msec in patients with ventricular conduction abnormalities), subsequent dosing should be adjusted as follows: Maintenance of TIKOSYN Therapy Renal function and QTc should be re-evaluated every three months or as medically warranted

Lab Monitoring for TIKOSYN:

• QTc interval: Determine QTc at 2-3 hours after the first dose and after each subsequent dose (for in-hospital doses 2-5) to assess for QTc prolongation.
• Renal function: Calculate creatinine clearance prior to the first dose and re-evaluate every three months or as medically warranted.
• Serum potassium: Maintain potassium levels within the normal range before and during TIKOSYN therapy.
• ECG monitoring: Continuously monitor patients by ECG for a minimum of three days or for a minimum of 12 hours after electrical or pharmacological conversion to normal sinus rhythm, whichever is greater 2.

From the Research

Tikosyn Lab Monitoring

• Dofetilide, also known as Tikosyn, is a class III antiarrhythmic agent that requires careful monitoring due to its potential to prolong the QT interval and increase the risk of torsades de pointes 3, 4, 5.
• The therapeutic blood level range of dofetilide is unknown, and monitoring of dofetilide blood levels is not available 3.
• Patients initiated or reinitiated on dofetilide should be hospitalized for a minimum of 3 days for continuous electrocardiographic monitoring, evaluation of renal function, and serum electrolytes 3, 6.
• Dose adjustments are required in patients with renal insufficiency, as approximately 80% of dofetilide is excreted in the urine 3, 5.
• The QTc interval should be monitored, and dofetilide should not be given or discontinued if the QTc is greater than 500 ms 5.
• Concomitant use of drugs that increase the plasma level of dofetilide is contraindicated, including cimetidine, ketoconazole, trimethoprim-sulfamethoxazole, and verapamil 6.
• Close monitoring of renal function, concomitant medications, and corrected QT interval is required when using dofetilide, especially in patients with congenital heart disease 7.