Initiation of TIKOSYN Therapy
Step 1. Electrocardiographic assessment: Prior to administration of the first dose, the QTc or QT must be checked using an average of 5–10 beats. If the QTc or QT is greater than 440 msec (500 msec in patients with ventricular conduction abnormalities), TIKOSYN is contraindicated. If heart rate is less than 60 beats per minute, QT interval should be used. Proceed to Step 2 if the QTc or QT is 440 msec. Patients with heart rates <50 beats per minute have not been studied.
Step 2. Calculation of creatinine clearance: Prior to the administration of the first dose, the patient's creatinine clearance must be calculated using the following formula:
creatinine clearance (male) = | (140-age) × actual body weight in kg 72 × serum creatinine (mg/dL) |
creatinine clearance (female) = | (140-age) × actual body weight in kg × 0.85 72 × serum creatinine (mg/dL) |
When serum creatinine is given in µmol/L, divide the value by 88.4 (1 mg/dL = 88.4 µmol/L).
Step 3. Starting Dose: The starting dose of TIKOSYN is determined as follows:
Calculated Creatinine Clearance | TIKOSYN Dose |
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>60 mL/min | 500 mcg twice daily |
40 to 60 mL/min | 250 mcg twice daily |
20 to <40 mL/min | 125 mcg twice daily |
<20 mL/min | Tikosyn is contraindicated in these patients |
Step 4. Administer the adjusted TIKOSYN dose and begin continuous ECG monitoring.
Step 5. At 2–3 hours after administering the first dose of Tikosyn, determine the QTc or QT (if heart rate is less than 60 beats per minute). If the QTc or QT has increased by greater than 15% compared to the baseline established in Step 1 OR if the QTc or QT is greater than 500 msec (550 msec in patients with ventricular conduction abnormalities), subsequent dosing should be adjusted as follows:
If the Starting Dose Based on Creatinine Clearance is: | | Then the Adjusted Dose (for QTc or QT Prolongation) is: |
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500 mcg twice daily | | 250 mcg twice daily |
250 mcg twice daily | | 125 mcg twice daily |
125 mcg twice daily | | 125 mcg once a day |
Step 6. At 2–3 hours after each subsequent dose of Tikosyn, determine the QTc or QT (if heart rate is less than 60 beats per minute) (for in-hospital doses 2–5). No further down titration of Tikosyn based on QTc or QT is recommended.
NOTE: If at any time after the second dose of Tikosyn is given the QTc or QT is greater than 500 msec (550 msec in patients with ventricular conduction abnormalities), Tikosyn should be discontinued.
Step 7. Patients are to be continuously monitored 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.
The steps described above are summarized in the following diagram:
Maintenance of TIKOSYN Therapy
Renal function and QTc or QT (if heart rate is less than 60 beats per minute) should be re-evaluated every three months or as medically warranted. If QTc or QT exceeds 500 milliseconds (550 msec in patients with ventricular conduction abnormalities), TIKOSYN therapy should be discontinued and patients should be carefully monitored until QTc or QT returns to baseline levels. If renal function deteriorates, adjust dose as described in Initiation of TIKOSYN Therapy, Step 3.