DOSAGE AND ADMINISTRATION
Refer to the manufacturer's manual for the
implantable pump approved for intrathecal infusion for specific instructions and
precautions for programming the pump and/or refilling the reservoir. There are
various pumps with varying reservoir volumes and there are various refill kits
available. It is important to be familiar with all of these products in order to
select the appropriate refill kit for the particular pump in use.
Screening Phase:
Prior to pump implantation and initiation of chronic infusion of LIORESAL
INTRATHECAL (baclofen injection), patients must demonstrate a positive clinical
response to a LIORESAL INTRATHECAL bolus dose administered intrathecally in a
screening trial. The screening trial employs LIORESAL INTRATHECAL at a
concentration of 50 mcg/mL. A 1 mL ampule (50 mcg/mL) is available for use in
the screening trial. 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 LIORESAL INTRATHECAL 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 8 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, for adult patients, 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 Cerebral Origin:
After the first 24 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% only 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 by 10-40%, but no
more than 40%, to maintain adequate symptom control. The daily dose may be
reduced by 10-20% 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 kink or dislodgement).
Maintenance dosage for long term continuous infusion of LIORESAL INTRATHECAL
(baclofen injection) has ranged from 12 mcg/day to 2003 mcg/day, with most
patients adequately maintained on 300 micrograms to 800 micrograms per day.
There is limited experience with daily doses greater than 1000 mcg/day.
Determination of the optimal LIORESAL INTRATHECAL dose requires individual
titration. The lowest dose with an optimal response should be used.
Spasticity of Cerebral 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 life
style 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).
Maintenance dosage for long term continuous infusion of LIORESAL INTRATHECAL
(baclofen injection) has ranged from 22 mcg/day to 1400 mcg/day, with most
patients adequately maintained on 90 micrograms to 703 micrograms per day. In
clinical trials, only 3 of 150 patients required daily doses greater than 1000
mcg/day.
Pediatric Patients: Use same dosing recommendations
for patients with spasticity of cerebral origin. Pediatric patients under 12
years seemed to require a lower daily dose in clinical trials. Average daily
dose for patients under 12 years was 274 mcg/day, with a range of 24 to 1199
mcg/day. Dosage requirement for pediatric patients over 12 years does not seem
to be different from that of adult patients. Determination of the optimal
LIORESAL INTRATHECAL dose requires individual titration. The lowest dose with an
optimal response should be used.
Potential need for dose adjustments in chronic use:
During long term treatment, approximately 5% (28/627) 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 LIORESAL INTRATHECAL over a 2 to 4 week period and switching to
alternative methods of spasticity management. After the “drug holiday,” LIORESAL
INTRATHECAL 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 upon the
total daily dose required as well as the delivery rate of the pump. LIORESAL
INTRATHECAL may require dilution when used with certain implantable pumps.
Please consult manufacturer's manual for specific recommendations.
Preparation Instruction:
Screening
Use the 1 mL screening ampule only (50 mcg/mL) for bolus injection into the
subarachnoid space. For a 50 mcg bolus dose, use 1 mL of the screening ampule.
Use 1.5 mL of 50 mcg/mL baclofen injection for a 75 mcg bolus dose. For the
maximum screening dose of 100 mcg, use 2 mL of 50 mcg/mL baclofen injection (2
screening ampules).
Maintenance
For patients who require concentrations other than 500 mcg/mL or 2000 mcg/mL,
LIORESAL INTRATHECAL must be diluted.
LIORESAL INTRATHECAL must be diluted with sterile
preservative free Sodium Chloride for Injection, U.S.P.
Delivery Regimen:
LIORESAL INTRATHECAL 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 LIORESAL
INTRATHECAL 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.
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