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Maintenance of Normal Sinus Rhythm (Delay in AF/AFl Recurrence)
TIKOSYN is indicated for the maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter [AF/AFl]) in patients with atrial fibrillation/atrial flutter of greater than one week duration who have been converted to normal sinus rhythm. Because TIKOSYN can cause life threatening ventricular arrhythmias, it should be reserved for patients in whom atrial fibrillation/atrial flutter is highly symptomatic.
In general, antiarrhythmic therapy for atrial fibrillation/atrial flutter aims to prolong the time in normal sinus rhythm. Recurrence is expected in some patients (see Clinical Studies).
Conversion of Atrial Fibrillation/Flutter
TIKOSYN has not been shown to be effective in patients with paroxysmal atrial fibrillation.
DOSAGE AND ADMINISTRATION
- Therapy with TIKOSYN must be initiated (and, if necessary, re-initiated) in a setting that provides continuous electrocardiographic (ECG) monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Patients should continue to be monitored in this way for a minimum of three days. Additionally, patients should not be discharged within 12 hours of electrical or pharmacological conversion to normal sinus rhythm.
- The dose of TIKOSYN must be individualized according to calculated creatinine clearance and QTc. (QT interval should be used if the heart rate is < 60 beats per minute. There are no data on use of TIKOSYN when the heart rate is < 50 beats per minute.) The usual recommended dose of TIKOSYN is 500 mcg BID, as modified by the dosing algorithm described below. For consideration of a lower dose, see Special Considerations below.
- Serum potassium should be maintained within the normal range before TIKOSYN treatment is initiated and should be maintained within the normal range while the patient remains on TIKOSYN therapy. (See WARNINGS, Hypokalemia and Potassium-Depleting Diuretics). In clinical trials, potassium levels were generally maintained above 3.6–4.0 mEq/L.
- Patients with atrial fibrillation should be anticoagulated according to usual medical practice prior to electrical or pharmacological cardioversion. Anticoagulant therapy may be continued after cardioversion according to usual medical practice for the treatment of people with AF. Hypokalemia should be corrected before initiation of TIKOSYN therapy (see WARNINGS, Ventricular Arrhythmia).
- Patients to be discharged on TIKOSYN therapy from an inpatient setting as described above must have an adequate supply of TIKOSYN, at the patient's individualized dose, to allow uninterrupted dosing until the patient receives the first outpatient supply.
- TIKOSYN is distributed only to those hospitals and other appropriate institutions confirmed to have received applicable dosing and treatment initiation education programs. Inpatient and subsequent outpatient discharge and refill prescriptions are filled only upon confirmation that the prescribing physician has received applicable dosing and treatment initiation education programs. For this purpose, a list for use by pharmacists is maintained containing hospitals and physicians who have received one of the education programs.
Instructions for Individualized Dose Initiation
Initiation of TIKOSYN Therapy
Step 1. Electrocardiographic assessment: Prior to administration of the first dose, the QTc must be determined using an average of 5–10 beats. If the QTc 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. 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) x actual body weight in kg|
|72 x serum creatinine (mg/dL)|
|creatinine clearance (female) =||(140-age) x actual body weight in kg x .85|
|72 x 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|
|> 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|
|i n 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. 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:
|If the Starting Dose Based on Creatinine Clearance is:||Then the Adjusted Dose (for QTc Prolongation) is:|
|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 (for in-hospital doses 2–5). No further down titration of TIKOSYN based on QTc is recommended.
NOTE: If at any time after the second dose of TIKOSYN is given the QTc 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 should be re-evaluated every three months or as medically warranted. If QTc exceeds 500 milliseconds (550 msec in patients with ventricular conduction abnormalities), TIKOSYN therapy should be discontinued and patients should be carefully monitored until QTc returns to baseline levels. If renal function deteriorates, adjust dose as described in Initiation of TIKOSYN Therapy, Step 3.
Consideration of a Dose Lower than that Determined by the Algorithm
The dosing algorithm shown above should be used to determine the individualized dose of TIKOSYN. In clinical trials (see Clinical Studies), the highest dose of 500 mcg BID of TIKOSYN as modified by the dosing algorithm led to greater effectiveness than lower doses of 125 or 250 mcg BID as modified by the dosing algorithm. The risk of Torsade de Pointes, however, is related to dose as well as to patient characteristics (see WARNINGS). Physicians, in consultation with their patients, may therefore in some cases choose doses lower than determined by the algorithm. It is critically important that if at any time this lower dose is increased, the patient needs to be rehospitalized for three days. Previous toleration of higher doses does not eliminate the need for rehospitalization.
The maximum recommended dose in patients with a calculated creatinine clearance greater than 60 mL/min is 500 mcg BID; doses greater than 500 mcg BID have been associated with an increased incidence of Torsade de Pointes.
A patient who misses a dose should NOT double the next dose. The next dose should be taken at the usual time.
If patients do not convert to normal sinus rhythm within 24 hours of initiation of TIKOSYN therapy, electrical conversion should be considered. Patients continuing on TIKOSYN after successful electrical cardioversion should continue to be monitored by electrocardiography for 12 hours post cardioversion, or a minimum of 3 days after initiation of TIKOSYN therapy, whichever is greater.
Switch to TIKOSYN from Class I or other Class III Antiarrhythmic Therapy
Before initiating TIKOSYN therapy, previous antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of three (3) plasma half-lives. Because of the unpredictable pharmacokinetics of amiodarone, TIKOSYN should not be initiated following amiodarone therapy until amiodarone plasma levels are below 0.3 mcg/mL or until amiodarone has been withdrawn for at least three months.
Stopping TIKOSYN Prior to Administration of Potentially Interacting Drugs
If TIKOSYN needs to be discontinued to allow dosing of other potentially interacting drug(s), a washout period of at least two days should be followed before starting the other drug(s).
TIKOSYN® 125 mcg (0.125 mg) capsules are supplied as No. 4 capsules with a light orange cap and white body, printed with TKN 125 PFIZER, and are available in:
TIKOSYN® 250 mcg (0.25 mg) capsules are supplied as No. 4 capsules, peach cap and body, printed with TKN 250 PFIZER, and are available in:
TIKOSYN® 500 mcg (0.5 mg) capsules are supplied as No. 2 capsules, peach cap and white body, printed with TKN 500 PFIZER, and are available in:
|125 mcg (0.125 mg)||250 mcg (0.25mg)||500 mcg (0.5mg)|
|Obverse||TKN 125||TKN 250||TKN 500|
|Bottle of 14||0069-5800-61||0069-5810-61||0069-5820-61|
|Bottle of 60||0069-5800-60||0069-5810-60||0069-5820-60|
|Unit dose / 40||0069-5800-43||0069-5810-43||0069-5820-43|
Store at controlled room temperature, 15° to 30°C (59° to 86°F).
PROTECT FROM MOISTURE AND HUMIDITY.
Dispense in tight containers (USP).
Distributed by : Pfizer Labs, Division of Pfizer Inc, NY, NY 10017. Revised February 2011
Last reviewed on RxList: 8/16/2011
This monograph has been modified to include the generic and brand name in many instances.
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