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Betapace Indications, Dosage, Storage, Stability - Sotalol
Betapace Indications, Dosage, Storage, Stability - Sotalol
INDICATIONS
Oral BETAPACE® (sotalolhydrochloride) is indicated for the
treatment of documented ventricular
arrhythmias, such as sustained
ventricular tachycardia,
that in the judgment
of the physician are
life-threatening. Because of the pro arrhythmic effects of BETAPACE®
(See WARNINGS), including
a 1.5 to 2% rate of torsade
de pointes or new VT/VF in patients with either NSVT or supraventricular
arrhythmias, its use in patients with less severe arrhythmias, even
if the patients are symptomatic,
is generally not recommended. Treatment of patients with asymptomatic
ventricular premature
contractions should be avoided.
Initiation of BETAPACE® treatment
or increasing doses, as with other antiarrhythmic agents used to
treat life-threatening arrhythmias, should be carried out in the
hospital. The response
to treatment should
then be evaluated by a suitable method
(e.g., PES or Holter monitoring) prior to continuing the patient
on chronic therapy.
Various approaches have been used to determine the response
to antiarrhythmic
therapy, including BETAPACE®.
In the ESVEM Trial, response
by Holter monitoring was tentatively defined as 100% suppression
of ventricular tachycardia,
90% suppression
of non-sustained VT, 80% suppression
of paired VPCs, and 75% suppression
of total VPCs in patients who had at least 10 VPCs/hour at baseline;
this tentative response
was confirmed if VT lasting 5 or more beats was not observed during
treadmill exercise testing using a standard
Bruce protocol. The PES protocol
utilized a maximum of
three extrastimuli at three pacing
cycle lengths and two
right ventricular pacing
sites. Response by PES was defined as prevention
of induction of the following: 1) monomorphic
VT lasting over 15 seconds; 2) non-sustained polymorphic
VT containing more than 15 beats of monomorphic VT in patients with
a history of monomorphic
VT; 3) polymorphic
VT or VF greater than 15 beats in patients with VF
or a history of aborted
sudden death without monomorphic
VT; and 4) two episodes of polymorphic
VT or VF of greater than 15 beats in a patient
presenting with monomorphic
VT. Sustained VT or NSVT producing hypotension
during the final treadmill
test was considered a drug
failure.
In a multicenter open-label long-term study of BETAPACE® in
patients with life-threatening ventricular
arrhythmias which had proven refractory to other anti-arrhythmic
medications, response
by Holter monitoring was defined as in ESVEM. Response by PES was
defined as non-inducibility of sustained VT by at least double
extrastimuli delivered at a pacing
cycle length of 400 msec. Overall survival
and arrhythmia recurrence
rates in this study were similar to those seen in ESVEM, although
there was no comparative
group to allow a definitive
assessment of outcome.
Antiarrhythmic drugs have not been shown to enhance survival
in patients with ventricular
arrhythmias.
DOSAGE AND ADMINISTRATION
As with other antiarrhythmic
agents, BETAPACE® should be initiated and doses increased in
a hospital with facilities
for cardiac rhythm
monitoring and assessment
(see INDICATIONS
AND USAGE). BETAPACE®
should be administered only after appropriate
clinical assessment
(see INDICATIONS
AND USAGE), and the dosage
of BETAPACE® must be individualized for each patient
on the basis of therapeutic
response and tolerance. Proarrhythmic events can occur not only
at initiation of therapy, but also with each upward dosage
adjustment.
Dosage of BETAPACE® should be adjusted gradually, allowing 2-3
days between dosing increments in order
to attain steady-state plasma
concentrations, and to allow monitoring of QT intervals. Graded
dose adjustment
will help prevent the usage
of doses which are higher than necessary to control
the arrhythmia. The recommended initial
dose is 80 mg
twice daily. This dose may be increased, if necessary, after appropriate
evaluation to 240
or 320 mg/day (120-160 mg
twice daily). In most patients,
a therapeutic response
is obtained at a total daily dose
of 160 to 320 mg/day, given in two or three divided doses. Some
patients with life-threatening refractory
ventricular arrhythmias may require doses as high as 480-640 mg/day;
however, these doses should only be prescribed when the potential
benefit outweighs the
increased risk of adverse
events, in particular proarrhythmia. Because of the long terminal
elimination half-life
of BETAPACE® dosing on more than a BID regimen
is usually not necessary.
DOSAGE IN RENAL IMPAIRMENT
Because sotalolis excreted predominantly in urine
and its terminal elimination half-life
is prolonged in conditions of renal
impairment, the dosing
interval (time between
divided doses) of sotalolshould be modified (when creatinine
clearance is lower
than 60 mL/min).
Since the terminal
elimination half-life
of BETAPACE® (sotalolhydrochloride) is increased in patients
with renal impairment,
a longer duration of
dosing is required to reach steady-state. Dose escalations in renal
impairment should be done after administration
of at least 5-6 doses at appropriate intervals.
chronic hemodialysis
is limited to six patients in two studies. In
these patients, terminal
elimination half
life is prolonged to 40
hours in the interdialysis period
and approaches 7 hours during dialysis. It is estimated that 20%-40%
of sotalolis removed during dialysis
and that a slight rebound
of plasma concentration
is noted post dialysis.
Extreme caution must be taken in dosing patients in renal
failure requiring hemodialysis,
usual parameters of safety and efficacy
(heart rate, QT interval
and control of arrythmia)
must be closely monitored.>
Extreme caution should be exercised in the use of sotalolin patients
with renal failure undergoing
hemodialysis. The half-life
of sotalolis prolonged (up to 69 hours) in anuric patients. Sotalol,
however, can be partly removed by dialysis
with subsequent partial rebound
in concentrations when dialysis is completed. Both safety (heart
rate, QT interval) and efficacy
(arrhythmia control) must be closely monitored.
Transfer to BETAPACE®
Before starting BETAPACE®, 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® should not be initiated
until the QT interval
is normalized (see WARNINGS).
HOW SUPPLIED
BETAPACE® (sotalolhydrochloride); capsule-shaped light-blue
scored tablets imprinted with the strength
and "BETAPACE", are available as follows:
NDC50419-105-10 80 mg strength,
bottle of 100
NDC50419-105-11 80 mg strength,
carton of 100 unit dose
NDC50419-109-10 120 mg strength,
bottle of 100
NDC50419-109-11 120 mg strength,
carton of 100 unit dose
NDC50419-106-10 160 mg strength,
bottle of 100
NDC50419-106-11 160 mg strength,
carton of 100 unit dose
NDC50419-107-10 240 mg strength,
bottle of 100
NDC50419-107-11 240 mg strength,
carton of 100 unit dose
Store at controlled room
temperature, between 15° to 30° C (59° to 86° F).
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