A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Tikosyn Indications, Dosage, Storage, Stability - Dofetilide
Tikosyn Indications, Dosage, Storage, Stability - Dofetilide
INDICATIONS
AND USES
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 TRIALS .)
Conversion of Atrial Fibrillation/Flutter
TIKOSYN is indicated for the conversion of atrial fibrillation and atrial flutter
to normal sinus rhythm.
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.
- 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 in-patient 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:
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:
|
creatinine clearance (male) =
|
(140-age) × body weight in kg
|
| |
72 × serum creatinine (mg/dL)
|
| |
|
|
creatinine clearance (female) =
|
(140-age) × body weight in kg × 0.85
|
| |
72 × serum creatinine (mg/dL)
|
| 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 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. 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.
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.
Special Considerations
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.
Cardioversion: 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).
HOW SUPPLIED
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 (0.25 mg)
|
500 mcg (0.5 mg)
|
|
Observe:
|
TKN 125
|
TKN 250
|
TKN 500
|
|
Reverse
|
PFIZER
|
PFIZER
|
PFIZER
|
|
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).
Rx only
Pfizer Labs
Division of Pfizer Inc, NY, NY 10017
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