INDICATIONS
Tablets
Baclofen is useful for the alleviation of signs and symptoms
of spasticity resulting from multiple sclerosis, particularly
for the relief of flexor spasms and concomitant pain,
clonus, and muscular rigidity. Patients should have reversible
spasticity so that baclofen treatment will aid in restoring
residual function.
Baclofen may also be of some value in patients with spinal
cord injuries and other spinal cord diseases.
Baclofen is not indicated in the treatment of skeletal
muscle spasm resulting from rheumatic disorders.
The efficacy of baclofen in stroke, cerebral palsy, and
Parkinson's disease has not been established and therefore,
it is not recommended for these conditions.
Injection
Baclofen injection is indicated for use in the management
of severe spasticity. Patients should first respond to
a screening dose of intrathecal baclofen prior to consideration
for long-term infusion via an implantable pump. For spasticity
of spinal cord origin, chronic infusion of baclofen intrathecal
via an implantable pump should be reserved for patients
unresponsive to oral baclofen therapy, or those who experience
intolerable CNS side effects at effective doses. Patients
with spasticity due to traumatic brain injury should wait
at least one year after the injury before consideration
of long-term intrathecal baclofen therapy. Baclofen injection
is intended for use by the intrathecal route in single
bolus test doses (via spinal catheter or lumbar puncture)
and for chronic use, only in implantable pumps approved
by the FDA specifically for the administration of baclofen
injection into the intrathecal space.
Spasticity of Spinal Cord Origin: Evidence supporting
the efficacy of baclofen injection was obtained in randomized,
controlled investigations that compared the effects of
either a single intrathecal dose or a three day intrathecal
infusion of baclofen injection to placebo. In patients
with severe spasticity and spasms due to either spinal
cord trauma or multiple sclerosis, baclofen injection
was superior to placebo on both principal outcome measures
employed: change from baseline in the Ashworth rating
of spasticity and the frequency of spasms.
Spasticity of Cerebral Origin: Evidence supporting the
efficacy of baclofen injection was obtained in randomized,
controlled investigations that compared the effects of
a single intrathecal dose of baclofen injection to placebo
in patients with severe spasticity associated with cerebral
palsy or brain injury. In both cases, an intrathecal dose
of baclofen injection was superior to a placebo in reducing
spasticity, as measured by the Ashworth scale. In patients
with brain injury, baclofen injection was superior to
placebo in both principal outcomes of change from baseline
in the Ashworth rating of spasticity and the frequency
of spasms.
Baclofen injection therapy may be considered an alternative
to destructive neurosurgical procedures. Prior to implantation
of a device for chronic intrathecal infusion of baclofen
intrathecal, patients must show a response to baclofen
injection in a screening trial (see
DOSAGE AND ADMINISTRATION
.)
DOSAGE AND ADMINISTRATION
Tablets
The determination of optimal dosage requires individual
titration. Start therapy at a low dosage and increase
gradually until optimum effect is achieved (usually between
40-80 mg daily).
The following dosage schedule is suggested:
5 mg t.i.d. for 3 days
10 mg t.i.d. for 3 days
15 mg t.i.d. for 3 days
20 mg t.i.d. for 3 days
Thereafter additional increases may be necessary but
the total daily dose should not exceed a maximum of 80
mg daily (20 mg q.i.d.).
The lowest dose compatible with an optimal response is
recommended. If benefits are not evident after a reasonable
trial period, patients should be slowly withdrawn from
the drug (see WARNINGS, Abrupt Drug Withdrawal).
Injection
Refer to the manufacturer's manual for the implantable
intrathecal infusion pump for specific instructions and
precautions for programming the pump and/or refilling
the reservoir.
Screening Phase: Prior to pump implantation
and initiation of chronic infusion of baclofen injection,
patients must demonstrate a positive clinical response
to a baclofen injection bolus dose administered intrathecally
in a screening trial. The screening trial employs baclofen
injection which must be diluted to a concentration of
50 mcg per ml. The screening procedure is as follows.
An initial bolus containing 50 micrograms in a volume
of 1 milliliter is administered into the intrathecal space
by barbotage over a period of not less than one minute.
The patient is observed over the ensuing 4 to 8 hours.
A positive response consists of a significant decrease
in muscle tone and/or frequency and/or severity of spasms.
If the initial response is less than desired, a second
bolus injection may be administered 24 hours after the
first. The second screening bolus dose consists of 75
micrograms in 1.5 milliliters. Again, the patient should
be observed for an interval of 4 to 8 hours. If the response
is still inadequate, a final bolus screening dose of 100
micrograms in 2 milliliters may be administered 24 hours
later.
Pediatric Patients: The starting screening
dose for pediatric patients is the same as in adult patients,
i.e., 50 mcg. However, for very small patients, a screening
dose of 25 mcg may be tried first.
Patients who do not respond to a 100 mcg intrathecal
bolus should not be considered candidates for an implanted
pump for chronic infusion.
Post-Implant Dose Titration Period:
To determine the initial total daily dose of baclofen
injection following implant, the screening dose that gave
a positive effect should be doubled and administered over
a 24-hour period, unless the efficacy of the bolus dose
was maintained for more than 12 hours, in which case the
starting daily dose should be the screening dose delivered
over a 24-hour period. No dose increases should be given
in the first 24 hours (i.e., until the steady state is
achieved).
Adult Patients with Spasticity of Spinal Cord
Origin: After the first 24 hours, the daily dosage
should be increased slowly by 10%-30% increments and only
once every 24 hours, until the desired clinical effect
is achieved.
Adult Patients with Spasticity of Spinal Cord
Origin: After the first 224 hours, the daily
dose should be increased slowly by 5-15% only once every
24 hours, until the desired clinical effect is achieved.
Pediatric Patients: After the first
24 hours, the daily dose should be increased slowly by
5-15% once every 24 hours, until the desired clinical
effect is achieved.
If there is not a substantive clinical response to increases
in the daily dose, check for proper pump function and
catheter patency.
Patients must be monitored closely in a fully equipped
and staffed environment during the screening phase and
dose-titration period immediately following implant. Resuscitative
equipment should be immediately available for use in case
of life-threatening or intolerable side effects.
Maintenance Therapy
Spasticity of Spinal Cord Origin Patients:
The clinical goal is to maintain muscle tone as close
to normal as possible, and to minimize the frequency and
severity of spasms to the extent possible, without inducing
intolerable side effects. Very often the maintenance dose
needs to be adjusted during the first few months of therapy
while patients adjust to changes in life style due to
the alleviation of spasticity. During periodic refills
of the pump, the daily dose may be increased 10-40%, but
no more than 40%, to maintain adequate symptom control.
The daily dose may be reduced by 10 to 20% if patients
experience side effects. Most patients require gradual
increases in dose over time to maintain optimal response
during chronic therapy. A sudden large requirement for
dose escalation suggests a catheter complication (i.e.,
catheter link or dislodgement).
Maintenance dosage for long term continuous infusion
of baclofen injection has ranged from 12 micrograms/day
to 1500 micrograms/day, with most patients adequately
maintained on 300 micrograms to 800 micrograms per day.
There is limited experience with daily doses greater than
1000 micrograms/day. Determination of the optimal baclofen
injection dose requires individual titration. The lowest
dose with an optimal response should be used.
Spasticity of Spinal Cord Origin patients:
The clinical goal is to maintain muscle tone as close
to normal as possible and to minimize the frequency and
severity of spasms to the extent possible, without inducing
intolerable side effects, or to titrate the dose to the
desired degree of muscle tone for optimal functions. Very
often, the maintenance dose needs to be adjusted during
the first few months of therapy while patients adjust
to changes in lifestyle due to the alleviation of spasticity.
During periodic refills of the pump, the daily dose may
be increased by 5-20%, but no more than 20% to maintain
adequate symptom control. The daily dose may be reduced
by 10-20% if patients experience side effects. Many patients
require gradual increases in dose over time to maintain
optimal response during chronic therapy. A sudden large
requirement for dose escalation suggests a catheter complication
(i.e., catheter kink or dislodgement).
Pediatric Patients
Potential need for dose adjustments in chronic
use
During long term treatment approximately 10% of patients
become refractory to increasing doses. There is not sufficient
experience to make firm recommendations for tolerance
treatment; however, this "tolerance" has been
treated on occasion, in hospital, by a "drug holiday"
consisting of the gradual reduction of baclofen injection
over a two week period and switching to alternative methods
of spasticity management. After a few days, sensitivity
to baclofen may return, and baclofen injection may be
restarted at the initial continuous infusion dose.
Stability
Parenteral drug products should be inspected for particulate
matter and discoloration prior to administration, whenever
solution and container permit.
Delivery Specifications
The specific concentration that should be used depends
on the total daily dose required as well as the delivery
rate of the pump. Baclofen injection may require dilution
when used with certain implantable pumps. Please consult
manufacturer's manual for specific recommendations.
Screening
Dilution Instruction: Both strengths of baclofen
injection (10 mg/5 ml and 10 mg/20 ml) must be diluted
to a 50 mcg/ml concentration for bolus injection into
the subarachnoid space.
Maintenance
For patients who require concentrations other than 500
mcg/ml or 2000 mcg/ml, baclofen injection must
be diluted.
Baclofen injection must be dilutedwith
sterile preservative free Sodium Chloride for Injection,
U.S.P.
Delivery Regimen
Baclofen injection is most often administered in a continuous
infusion mode immediately following implant. For those
patients implanted with programmable pumps who have achieved
relatively satisfactory control on continuous infusion,
further benefit may be attained using more complex schedules
of baclofen injection delivery. For example, patients
who have increased spasms at night may require a 20% increase
in their hourly infusion rate. Changes in flow rate should
be programmed to start two hours before the time of desired
clinical effect.
HOW SUPPLIED
Tablets: Dispense in a tight container.
Injection: Does not require refrigeration.
Do not freeze. Do not heat sterilize.
Storage: Do not store above 86°F
(30°C).
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