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
Betapace Indications, Dosage, Storage, Stability - Sotalol Hydrochloride
Betapace Indications, Dosage, Storage, Stability - Sotalol Hydrochloride
INDICATIONS
AND USAGE
BETAPACE AFTM is indicated for the maintenance of
normal sinus rhythm [delay in time to recurrence of atrial fibrillation/atrial
flutter (AFIB/AFL)] in patients with symptomatic AFIB/AFL who are currently
in sinus rhythm. Because BETAPACE AFTM can cause life-threatening
ventricular arrhythmias, it should be reserved for patients in whom AFIB/AFL
is highly symptomatic. Patients with paroxysmal AFIB whose AFIB/AFL that is
easily reversed (by Valsalva maneuver, for example) should usually not be given
BETAPACE AFTM (See WARNINGS).
In general, antiarrhythmic therapy for AFIB/AFL aims to prolong
the time in normal sinus rhythm. Recurrence is expected in some patients (See
CLINICAL STUDIES).
Sotalol is also indicated for the treatment of documented life-threatening
ventricular arrhythmias and is marketed under the brand name BETAPACEÒ
(sotalol hydrochloride). BETAPACE however, must
not be substituted for BETAPACE AFTM because of significant differences
in labeling (i.e. patient package insert, dosing administration and safety information).
DOSAGE AND ADMINISTRATION
· Therapy with BETAPACE
AFTM must be initiated (and, if necessary, titrated) 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 3
days on the maintenance dose. In addition, patients should not be discharged
within 12 hours of electrical or pharmacological conversion to normal sinus
rhythm.
· The QT interval
is used to determine patient eligibility for BETAPACE AFTM treatment
and for monitoring safety during treatment. The baseline QT interval must
be £450 msec in order for a patient to
be started on BETAPACE AFTM therapy. During initiation and titration,
the QT interval should be monitored 2-4 hours after each dose. If the QT
interval prolongs to 500 msec or greater, the dose must be reduced or the
drug discontinued.
· The dose of BETAPACE
AFTM must be individualized according to creatinine clearance.
In patients with a creatinine clearance > 60 mL/min BETAPACE AFTM
is administered twice daily (BID) while in those with a creatinine clearance
between 40 and 60 mL/min, the dose is administered once daily (QD). In patients
with a creatinine clearance less than 40 mL/min BETAPACE AFTM
is contraindicated. The recommended initial dose of BETAPACE AFTM
is 80 mg and is initiated as shown in the dosing algorithm described below.
The 80 mg dose can be titrated upward to 120 mg during initial hospitalization
or after discharge on 80 mg in the event of recurrence, by rehospitalization
and repeating the same steps used during the initiation of therapy (see
Upward Titration of Dose).
· Patients with atrial
fibrillation should be anticoagulated according to usual medical practice.
Hypokalemia should be corrected before initiation of BETAPACE AFTM
therapy (see WARNINGS, Ventricular
Arrhythmia).
· Patients to be discharged
on BETAPACE AFTM therapy from an in-patient setting should have
an adequate supply of BETAPACE AFTM to allow uninterrupted therapy
until the patient can fill a BETAPACE AFTM prescription.
Initiation of BETAPACE AFTM Therapy
Step 1. Electrocardiographic assessment: Prior to administration
of the first dose, the QT interval must be determined using an average of 5
beats. If the baseline QT is greater than 450 msec (JT ³
330 msec if QRS over 100 msec) , BETAPACE AFTM is contraindicated.
Step 2: Calculation of creatinine clearance: Prior to
the administration of the first dose, the patient’s creatinine clearance should
be calculatedusing the following formula:
creatinine clearance (male) = (140-age) x body weight in
kg
72 x serum creatinine (mg/dL)
creatinine clearance (female) = (140-age) x body weight
in kg x 0.85
72 x serum creatinine (mg/dL)
When serum creatinine is given in mmol/L,
divide the value by 88.4 (1 mg/dL = 88.4 mmol/L)
Step 3. Starting Dose: The starting dose of BETAPACE
AFTM is 80 mg twice daily (BID) if the creatinine clearance is >
60 mL/min, and 80 mg once daily (QD) if the creatinine clearance is 40-60 mL/min.
If the creatinine clearance is < 40 mL/min BETAPACE AFTM is contraindicated.
Step 4. Administer the appropriate daily dose of BETAPACE
AFTM and begin continuous ECG monitoring with QT interval measurements
2-4 hours after each dose.
Step 5. If the 80 mg dose level is tolerated and the
QT interval remains < 500 msec after at least 3 days (after 5 or 6 doses
if patient receiving QD dosing), the patient can be discharged. Alternatively,
during hospitalization, the dose can be increased to 120 mg bid and the patient
followed for 3 days on this dose (followed for 5 or 6 doses if patient receiving
QD doses).
The steps described above are summarized in the following
|
Place Patient on Telemetry
|
|
Check Baseline QT If QT > 450 msec BETAPACE AF™
is CONTRAINDICATED If QT £450
msec, proceed
|
|
Calculate Creatinine Clearance (Clcr) If Clcr is <
40 mL/min BETAPACE AF™ is CONTRAINDICATED If Clcr is 40-60
mL/min start BETAPACE AF™ 80 mg QD If Clcr is > 60 mL/min start
BETAPACE AF™ 80 mg BID
|
|
Monitor QT 2-4 hours after each dose. If QT ³
500 msec discontinue BETAPACE AF™. If QT < 500 msec after 3 days
(after 5th or 6th dose if patient receiving QD dosing) discharge patient
on current treatment. Alternatively, during hospitalization, the dose
can be increased to 120 mg bid and the patient followed for 3 days on
this dose (followed for 5 or 6 doses if patient receiving QD doses).
|
diagram:
Upward Titration of Dose
If the 80 mg dose level (given BID or QD depending upon the
creatinine clearance) does not reduce the frequency of relapses of AFIB/AFL
and is tolerated without excessive QT
interval prolongation (i.e. ³
520 msec), the dose level may be increased to 120 mg (BID or QD depending upon
the creatinine clearance). As proarrhythmic events can occur not only at initiation
of therapy, but also with each upward dosage adjustment, Steps 2 through 5 used
during initiation of BETAPACE AFTM therapy should be followed when
increasing the dose level. In the U.S. multicenter dose-response study, the
120 mg dose (BID or QD) was found to be the most effective in prolonging the
time to ECG documented symptomatic recurrence of AFIB/AFL. If the 120 mg dose
does not reduce the frequency of early relapse of AFIB/AFL and is tolerated
without excessive QT interval prolongation (³520
msec), an increase to 160 mg (BID or QD depending upon the creatinine clearance
can be considered. Steps 2 through 5 used during the initiation of therapy should
be used again to introduce such an increase.
Maintenance of BETAPACE AFTM Therapy
Renal function and QT should be re-evaluated regularly if medically
warranted. If QT is
520 msec or greater (JT 430 msec or greater if QRS is >
100 msec), the dose of BETAPACE AFTM therapy should be reduced and
patients should be carefully monitored
until QT returns to less than 520 msec. If the QT interval
is ³ 520 msec while on the lowest maintenance
dose level (80 mg) the drug should be discontinued. If renal function
deteriorates, reduce the daily dose in half by administering
the drug once daily as described in Initiation of BETAPACE AFTM
Therapy, Step 3.
Special Considerations
The maximum recommended dose in patients with a calculated
creatinine clearance greater than 60 mL/min is 160 mg BID, doses greater than
160 mg BID have been associated with an increased incidence of torsade de pointes
and are not recommended. A patient who misses a dose should NOT double the next
dose. The next dose should be taken at the usual time.
Transfer to BETAPACE AFTM from Betapace®
Patients with a history of symptomatic AFIB/AFL who are currently
receiving Betapace® for the maintenance of normal sinus rhythm
must should be transferred to BETAPACE AFTM because of the significant
differences in labeling (i.e., patient package insert, dosing administration,
and safety information).
Transfer to BETAPACE AFTM from Other Antiarrhythmic
Agents
Before starting BETAPACE AFTM, previous antiarrhythmic
therapy should generally be withdrawn under careful monitoring for a minimum
of 2-3 plasma half-lives if the patient’s clinical condition permits (see DRUG
INTERACTIONS). Treatment has been initiated in some patients receiving
I.V. lidocaine without ill effect. After discontinuation of amiodarone, BETAPACE
AFTM should not be initiated until the QT interval is normalized
(see WARNINGS).
HOW SUPPLIED
BETAPACE AFTM (sotalol hydrochloride); capsule-shaped
white scored tablets imprinted with the strength and "BERLEX" are
available as follows:
NDC 50419-115-06 80 mg strength, bottle of 60 in
unit use package NDC 50419-119-06 120 mg strength, bottle of 60 in
unit use package NDC 50419-116-06 160 mg strength, bottle of 60 in
unit use package NDC 50419-115-11 80 mg strength, carton of 100 unit
dose
NDC 50419-119-11 120 mg strength, carton of 100
unit dose
NDC 50419-116-11 160 mg strength, carton of 100
unit dose
Store at 25ºC with excursions permitted between 15º-30ºC.
Rx only
© 2000, Berlex Laboratories. All rights
reserved.
Manufactured by: Berlex® Laboratories,
Wayne, NJ 07470
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