Precautions for Using Tikosyn (Dofetilide) in Patients with QT Interval Prolongation
Tikosyn (dofetilide) is absolutely contraindicated in patients with pre-existing QT prolongation (QTc >440 msec or >500 msec with ventricular conduction abnormalities) due to the high risk of developing torsades de pointes. 1
Risk Assessment and Monitoring Requirements
Initial Evaluation
- Baseline QTc must be measured using an average of 5-10 beats
- Creatinine clearance must be calculated to determine appropriate dosing
- Electrolytes (especially potassium and magnesium) must be checked and corrected before initiation
Mandatory Hospitalization
- All patients must be hospitalized for a minimum of 3 days when:
- Starting Tikosyn
- Restarting after interruption
- Increasing the dose
- Switching from another antiarrhythmic
Dosing Based on Renal Function
- Creatinine clearance >60 mL/min: 500 mcg twice daily
- Creatinine clearance 40-60 mL/min: 250 mcg twice daily
- Creatinine clearance 20-<40 mL/min: 125 mcg twice daily
- Creatinine clearance <20 mL/min: Contraindicated 1
QT Monitoring Protocol
- ECG monitoring must be continuous during hospitalization
- QTc must be measured 2-3 hours after each dose
- Dose reduction required if:
- QTc increases >15% from baseline
- QTc exceeds 500 msec (550 msec with ventricular conduction abnormalities)
- Discontinue if QTc remains >500 msec after dose adjustment 1, 2
Risk Factors for Torsades de Pointes
Patients with the following risk factors require extra caution or avoidance of Tikosyn:
- Female gender
- Advanced age
- Heart disease (especially LV hypertrophy, ischemia, or low ejection fraction)
- Bradycardia or heart block
- Electrolyte abnormalities (hypokalemia, hypomagnesemia)
- Renal dysfunction
- Concomitant use of QT-prolonging medications
- History of torsades de pointes
- Starvation diet 2, 3
Contraindicated Medications
The following medications are absolutely contraindicated with Tikosyn:
- Verapamil
- Trimethoprim-containing medications (including TMP/SMX)
- Hydrochlorothiazide
- Cimetidine
- Dolutegravir
- Itraconazole
- Ketoconazole
- Megestrol
- Prochlorperazine 3
Long-term Management
- Renal function and QTc must be re-evaluated every three months
- Potassium levels should be maintained above 3.6-4.0 mEq/L
- Avoid potassium-depleting diuretics; consider loop diuretics if needed
- Discontinue if QTc exceeds 500 msec during follow-up
- Washout period of at least 2 days before starting potentially interacting drugs 1, 2
Managing Missed Doses
- If a dose is missed, the patient should NOT double the next dose
- The next dose should be taken at the usual time 1
Real-world Considerations
Recent studies show that QT prolongation requiring Tikosyn discontinuation occurs in approximately 17-19% of patients in real-world settings, significantly higher than the <3% reported in clinical trials 4. Concomitant use of other QT-prolonging drugs nearly doubles the risk of requiring discontinuation (31% vs 15%) 4.
Special Situations
Acute Ischemia
Patients experiencing acute myocardial ischemia while on Tikosyn are at particularly high risk for QT prolongation and torsades de pointes, even if they previously tolerated the medication well 5.
Diuretic Therapy
Diuretic therapy for acute heart failure is an independent risk factor for Tikosyn-related torsades de pointes (adjusted odds ratio 8.42) 6. Monitor renal function and electrolytes closely if diuretics are required.
Rapid Atrial Fibrillation
Patients with underlying AF and rapid ventricular rates have significantly increased risk of QT-related complications (adjusted odds ratio 16.95), likely due to difficulty in accurately measuring the QT interval 6.
By strictly adhering to these precautions, the risk of Tikosyn-induced torsades de pointes can be minimized while still providing effective antiarrhythmic therapy for appropriately selected patients.