What are the monitoring requirements for patients on Tikosyn (dofetilide)?

Tikosyn (Dofetilide) Monitoring Requirements

Dofetilide requires mandatory inpatient continuous ECG monitoring for a minimum of 3 days during initiation due to FDA requirements, with specific protocols for QTc assessment, renal function monitoring, and electrolyte management to prevent life-threatening torsades de pointes. 1, 2

Mandatory Inpatient Initiation Protocol

Initial Hospitalization Requirements

• All patients must be hospitalized for continuous ECG monitoring for at least 3 days when starting dofetilide, as mandated by the FDA due to the risk of QT prolongation and ventricular arrhythmias 1, 2
• Continuous telemetry monitoring is required throughout the entire initiation period 3, 4
• If electrical or pharmacological cardioversion occurs during initiation, monitoring must continue for a minimum of 12 hours post-cardioversion OR 3 days from initiation, whichever is greater 2

Pre-Initiation Assessment (Before First Dose)

Step 1: Baseline QTc Measurement

• Obtain baseline QTc using an average of 5-10 beats on ECG 2
• Dofetilide is contraindicated if baseline QTc >440 msec (>500 msec in patients with ventricular conduction abnormalities) 2
• For heart rates <60 bpm, use QT interval instead of QTc 2
• Patients with heart rates <50 bpm have not been studied and should be approached with extreme caution 2

Step 2: Renal Function Assessment

• Calculate creatinine clearance using the Cockcroft-Gault formula before the first dose 2
• Dofetilide is contraindicated in patients with creatinine clearance <20 mL/min 2
• Dosing is adjusted based on creatinine clearance: 500 mcg BID for CrCl >60 mL/min, 250 mcg BID for CrCl 40-60 mL/min, and 125 mcg BID for CrCl 20-40 mL/min 2

Step 3: Electrolyte Correction

• Correct hypokalemia before initiating dofetilide 2
• Measure and correct serum potassium and magnesium concentrations 1
• In clinical trials, potassium levels were maintained above 3.6-4.0 mEq/L 2

During Initiation Monitoring

QTc Monitoring at 2-3 Hours After Each Dose

• Measure QTc at 2-3 hours after administering each of the first 5 doses 2
• If QTc increases by >15% from baseline OR exceeds 500 msec (550 msec with ventricular conduction abnormalities), reduce the dose 2
• Dose reduction protocol: 500 mcg BID → 250 mcg BID; 250 mcg BID → 125 mcg BID; 125 mcg BID → 125 mcg once daily 2
• Discontinue dofetilide immediately if QTc exceeds 500 msec (550 msec with conduction abnormalities) at any time after the second dose 2

Risk of Torsades de Pointes

• The incidence of torsades de pointes during inpatient loading ranges from 0.8-1.5% with oral administration and 3-4% with IV administration 4
• In a large cohort study, 1.2% of patients developed torsades de pointes during loading, with 10 patients requiring resuscitation for cardiac arrest 5
• Risk factors for torsades de pointes include female sex, 500 mcg dose, reduced ejection fraction, and significant QTc increase from baseline 5

Outpatient Maintenance Monitoring

Regular Follow-Up Schedule

Every 3 Months (or More Frequently if Indicated)

• Obtain 12-lead ECG to assess rhythm and calculate QTc 1
• Measure serum potassium and magnesium concentrations 1
• Assess serum creatinine and recalculate creatinine clearance 1
• More frequent monitoring is required for patients taking other QT-prolonging drugs or those with changing renal function 1

Criteria for Discontinuation or Dose Adjustment

• Discontinue dofetilide if QTc exceeds 500 msec (550 msec with ventricular conduction abnormalities) and monitor carefully until QTc returns to baseline 2
• If renal function deteriorates, adjust dose according to the creatinine clearance-based dosing algorithm 2
• Correct any electrolyte abnormalities promptly, particularly hypokalemia and hypomagnesemia 1

Critical Safety Considerations

Drug Interactions and Contraindications

• Avoid all drugs that interfere with renal elimination or metabolism of dofetilide 3
• Dofetilide can be co-administered with digoxin and beta-blockers 3
• Other antiarrhythmic drugs must be avoided 3
• If switching from amiodarone, wait until amiodarone plasma levels are <0.3 mcg/mL or amiodarone has been withdrawn for at least 3 months 2

Rehospitalization Requirements

• If a patient on a lower dose requires dose escalation, mandatory rehospitalization for 3 days is required, even if the patient previously tolerated higher doses 2
• If dofetilide is discontinued to allow other potentially interacting drugs, a washout period of at least 2 days is required before starting the other medication 2

High-Risk Populations

• Women are at higher risk for torsades de pointes 4
• Patients with bradycardia, hypokalemia, hypomagnesemia, and renal dysfunction require particularly careful monitoring 4
• Patients with reduced ejection fraction have increased risk of adverse events 5

Long-Term Safety Data

• In a large cohort study, one-year all-cause mortality was higher in patients who continued dofetilide compared to those who discontinued (hazard ratio 2.48) 5
• Patients who experienced torsades de pointes had significantly higher one-year mortality (17.6% vs 3%) 5
• At 3-year follow-up in adults with congenital heart disease, 49% remained on dofetilide, with discontinuation primarily due to waning effect (57%) or side effects (18%) 6