BACLOFEN- baclofen injection
MAlA Pharmaceuticals, Inc.
Abrupt discontinuation of intrathecal baclofen, regardless of the cause, has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure and death.
Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the early symptoms of baclofen withdrawal. Special attention should be given to patients at apparent risk (e.g., spinal cord injuries at T-6 or above, communication difficulties, history of withdrawal symptoms from oral or intrathecal baclofen). Consult the technical manual of the implantable infusion system for additional post-implant clinician and patient information [see Warnings and Precautions (5.4)].
Baclofen injection is indicated for use in the management of severe spasticity in adult and pediatric patients age 4 years and above. 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 injection 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 with the Medtronic SynchroMed® II Programmable Pump or other pumps labeled for intrathecal administration of baclofen injection [see Clinical Studies (14)].
Prior to implantation of a device for chronic intrathecal infusion of baclofen injection, patients must show a response to baclofen injection in a screening trial [see Dosage and Administration (2.2)].
2.1 Use Only with Medtronic SynchroMed® II Programmable Pump (or other pumps labeled for intrathecal administration of baclofen injection)
Baclofen injection is approved only for use with the Medtronic SynchroMed® II Programmable Pump or other pumps labeled for intrathecal administration of baclofen injection. Refer to the manufacturer’s manual for specific instructions and precautions for programming the pump and/or refilling the reservoir. It is important to select the appropriate refill kit for the pump used to administer baclofen injection. Baclofen injection is not to be compounded with other medications.
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 at a concentration of 50 mcg/mL. A 1 mL syringe (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.
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.
Use the 1 mL screening syringe only (50 mcg/mL) for bolus injection into the subarachnoid space. For a 50 mcg bolus dose, use 1 mL of the screening syringe. 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 syringes).
The specific concentration that should be used depends upon the total daily dose required as well as the delivery rate of the pump. For patients who require concentrations other than 500 mcg/mL, 1,000 mcg/mL or 2,000 mcg/mL, baclofen injection must be diluted with sterile preservative free Sodium Chloride for Injection, USP.
Parenteral drug products should be inspected for particulate matter and discoloration prior to administration, whenever solution and container permit.
The external surface of baclofen injection prefilled syringes (all strengths, including the 50 mcg/mL strength) are non-sterile. The use of baclofen injection prefilled syringe in an aseptic setting (i.e., operating room) to fill sterile intrathecal pumps prior to implantation in patients is not recommended. For outpatient use, modify aseptic procedures to avoid contamination of sterile surfaces through contact with the non-sterile exterior of the baclofen injection prefilled syringe when filling the pump reservoir [see Warnings and Precautions (5.2)].
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.
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 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). In most patients, it will be necessary to increase the dose gradually over time to maintain effectiveness; a sudden requirement for substantial dose escalation typically indicates a catheter complication (i.e., catheter kink or dislodgement).
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% to 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% to 15% only once every 24 hours, until the desired clinical effect is achieved.
After the first 24 hours, the daily dose should be increased slowly by 5% to 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.
Additional Considerations Pertaining to Dosage Adjustment
Careful dose titration of baclofen injection is needed when spasticity is necessary to sustain upright posture and balance in locomotion or whenever spasticity is used to obtain optimal function and care. It may be important to titrate the dose to maintain some degree of muscle tone and allow occasional spasms to: 1) help support circulatory function, 2) possibly prevent the formation of deep vein thrombosis, 3) optimize activities of daily living and ease of care.
Except in overdose related emergencies, the dose of baclofen injection should ordinarily be reduced slowly if the drug is discontinued for any reason.
An attempt should be made to discontinue concomitant oral antispasticity medication to avoid possible overdose or adverse drug interactions, either prior to screening or following implant and initiation of chronic baclofen injection infusion. Reduction and discontinuation of oral antispasmotics should be done slowly and with careful monitoring by the physician. Abrupt reduction or discontinuation of concomitant antispastics should be avoided.
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