DailyMed Label: Baclofen (Intrathecal)

DailyMed Label: Baclofen (Intrathecal)

2023

DailyMed Prescription

Baclofen (Intrathecal)

baclofen

MAIA Pharmaceuticals, Inc.

NDC: 70511-122

NDC: 70511-124

NDC: 70511-122

NDC: 70511-122

NDC: 70511-124

NDC: 70511-124

Baclofen injection (intrathecal), USP is a muscle relaxant and antispastic. Its chemical name is 4-amino-3-(4-chlorophenyl) butanoic acid, and its structural formula is: Baclofen is a white to off-white, odorless or practically odorless crystalline powder, with a molecular weight of 213.66. It is slightly soluble in water, very slightly soluble in methanol, and insoluble in chloroform. Baclofen injection (intrathecal), USP is a sterile, pyrogen-free, isotonic solution free of antioxidants, preservatives or other potentially neurotoxic additives indicated only for intrathecal administration. The drug is stable in solution at 37° C and compatible with CSF. Each milliliter of baclofen injection (intrathecal) contains baclofen U. S. P., 500 mcg or 2,000 mcg and sodium chloride 9 mg in Water for Injection; pH range is 5.0 to 7.0. Each vial is intended for SINGLE USE ONLY. Discard any unused portion.  DO NOT AUTOCLAVE . baclofen-01

Baclofen injection (intrathecal) 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 injection (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 (intrathecal) 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 (intrathecal) into the intrathecal space. Spasticity of Spinal Cord Origin: Evidence supporting the efficacy of baclofen injection (intrathecal) 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 (intrathecal) to placebo in patients with severe spasticity and spasms due to either spinal cord trauma or multiple sclerosis. Baclofen injection (intrathecal) 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: The efficacy of baclofen injection (intrathecal) was investigated in three controlled clinical trials; two enrolled patients with cerebral palsy and one enrolled patients with spasticity due to previous brain injury. The first study, a randomized controlled cross-over trial of 51 patients with cerebral palsy, provided strong, statistically significant results; baclofen injection (intrathecal) was superior to placebo in reducing spasticity as measured by the Ashworth Scale. A second cross-over study was conducted in 11 patients with spasticity arising from brain injury. Despite the small sample size, the study yielded a nearly significant test statistic (p= 0.066) and provided directionally favorable results. The last study, however, did not provide data that could be reliably analyzed. Baclofen injection (intrathecal) therapy may be considered an alternative to destructive neurosurgical procedures. Prior to implantation of a device for chronic intrathecal infusion of baclofen injection (intrathecal), patients must show a response to baclofen injection (intrathecal) in a screening trial (see 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 Baclofen Injection (Intrathecal), patients must demonstrate a positive clinical response to a Baclofen Injection (Intrathecal) bolus dose administered intrathecally in a screening trial. The screening trial employs Baclofen Injection (Intrathecal) at a concentration of 50 mcg per mL.  A 1 mL ampule (50 mcg per 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 Baclofen Injection (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 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. Pediatric Patients: 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. 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 to 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 kink or dislodgement). Maintenance dosage for long term continuous infusion of Baclofen Injection (Intrathecal) 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 Baclofen Injection (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 to 20%, but no more than 20%, to maintain adequate symptom  control. The daily dose may be reduced by 10 to 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 Baclofen Injection (Intrathecal) 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 Baclofen Injection (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 Baclofen Injection (Intrathecal) over a 2 to 4 week period and switching to alternative methods of spasticity management. After the “drug holiday,” Baclofen Injection (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. Baclofen Injection (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 per 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 per mL Baclofen Injection (Intrathecal) for a 75 mcg bolus dose. For the maximum screening dose of 100 mcg, use 2 mL of 50 mcg per mL Baclofen Injection (Intrathecal) (2 screening ampules). Maintenance For patients who require concentrations other than 500 mcg per mL or 2000 mcg per mL, Baclofen Injection (Intrathecal) must be diluted. Baclofen Injection (Intrathecal) must be diluted with sterile preservative free Sodium Chloride for Injection, U.S.P. Delivery Regimen: Baclofen Injection (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 Baclofen Injection (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.

Hypersensitivity to baclofen. Baclofen injection (intrathecal) is not recommended for intravenous, intramuscular, subcutaneous or epidural administration.

Children should be of sufficient body mass to accommodate the implantable pump for chronic infusion. Please consult pump manufacturer's manual for specific recommendations. Safety and effectiveness in pediatric patients below the age of 4 have not been established. Screening Patients should be infection-free prior to the screening trial with baclofen injection (intrathecal) because the presence of a systemic infection may interfere with an assessment of the patient’s response to bolus baclofen injection (intrathecal). Pump Implantation Patients should be infection-free prior to pump implantation because the presence of infection may increase the risk of surgical complications. Moreover, a systemic infection may complicate dosing. Pump Dose Adjustment and Titration 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). Reservoir refilling must be performed by fully trained and qualified personnel following the directions provided by the pump manufacturer. Inadvertent injection into the subcutaneous tissue can occur if the reservoir refill septum is not properly accessed. Subcutaneous injection may result in symptoms of a systemic overdose or early depletion of the reservoir. Refill intervals should be carefully calculated to prevent depletion of the reservoir, as this would result in the return of severe spasticity and possibly symptoms of withdrawal. Strict aseptic technique in filling is required to avoid bacterial contamination and serious infection. A period of observation appropriate to the clinical situation should follow each refill or manipulation of the drug reservoir. Extreme caution must be used when filling an FDA approved implantable pump equipped with an injection port that allows direct access to the intrathecal catheter. Direct injection into the catheter through the catheter access port may cause a life-threatening overdose. Additional considerations pertaining to dosage adjustment: 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 (intrathecal) 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 (intrathecal) infusion. Reduction and discontinuation of oral anti-spasmotics should be done slowly and with careful monitoring by the physician. Abrupt reduction or discontinuation of concomitant antispastics should be avoided. Drowsiness: Drowsiness has been reported in patients on baclofen injection (intrathecal).  Patients should be cautioned regarding the operation of automobiles or other dangerous machinery, and activities made hazardous by decreased alertness. Patients should also be cautioned that the central nervous system depressant effects of baclofen injection (intrathecal) may be additive to those of alcohol and other CNS depressants. Intrathecal mass: Cases of intrathecal mass at the tip of the implanted catheter have been reported, most of them involving pharmacy compounded analgesic admixtures. The most frequent symptoms associated with intrathecal mass are: 1) decreased therapeutic response (worsening spasticity, return of spasticity when previously well controlled, withdrawal symptoms, poor response to escalating doses, or frequent or large dosage increases), 2) pain, 3) neurological deficit/dysfunction. Clinicians should monitor patients on intraspinal therapy carefully for any new neurological signs or symptoms. In patients with new neurological signs or symptoms suggestive of an intrathecal mass, consider a neurosurgical consultation, since many of the symptoms of inflammatory mass are not unlike the symptoms experienced by patients with severe spasticity from their disease. In some cases, performance of an imaging procedure may be appropriate to confirm or rule-out the diagnosis of an intrathecal mass. Precautions in special patient populations: Careful dose titration of baclofen injection (intrathecal) 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. Patients suffering from psychotic disorders, schizophrenia, or confusional states should be treated cautiously with baclofen injection (intrathecal) and kept under careful surveillance, because exacerbations of these conditions have been observed with oral administration. Baclofen injection (intrathecal) should be used with caution in patients with a history of autonomic dysreflexia. The presence of nociceptive stimuli or abrupt withdrawal of baclofen injection (intrathecal) may cause an autonomic dysreflexic episode. Because baclofen injection (intrathecal) is primarily excreted unchanged by the kidneys, it should be given with caution in patients with impaired renal function and it may be necessary to reduce the dosage. LABORATORY TESTS No specific laboratory tests are deemed essential for the management of patients on baclofen injection (intrathecal). DRUG INTERACTIONS There is inadequate systematic experience with the use of baclofen injection (intrathecal) in combination with other medications to predict specific drug-drug interactions. Interactions attributed to the combined use of baclofen injection (intrathecal) and epidural morphine include hypotension and dyspnea. CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY No increase in tumors was seen in rats receiving baclofen orally for two years. Adequate genotoxicity assays of baclofen have not been performed. PREGNANCY There are no adequate and well-controlled studies in pregnant women. In animal studies, baclofen had adverse effects on embryofetal development when administered orally to pregnant rats. Baclofen injection (intrathecal) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Baclofen given orally increased the incidence of fetal structural abnormalities (omphaloceles) in rats. Reductions in food intake and body weight gain were observed in the dams. Fetal structural abnormalities were not observed in mice or rabbits. NURSING MOTHERS In mothers treated with oral Baclofen (baclofen USP) in therapeutic doses, the active substance passes into the milk. It is not known whether detectable levels of drug are present in milk of nursing mothers receiving baclofen injection (intrathecal). As a general rule, nursing should be undertaken while a patient is receiving baclofen injection (intrathecal) only if the potential benefit justifies the potential risks to the infant. PEDIATRIC USE Children should be of sufficient body mass to accommodate the implantable pump for chronic infusion. Please consult pump manufacturer's manual for specific recommendations. Safety and effectiveness in pediatric patients below the age of 4 have not been established. Considerations based on experience with oral Baclofen (baclofen USP) A dose-related increase in incidence of ovarian cysts was observed in female rats treated chronically with oral Baclofen. Ovarian cysts have been found by palpation in about 4% of the multiple sclerosis patients who were treated with oral Baclofen for up to one year. In most cases these cysts disappeared spontaneously while patients continued to receive the drug. Ovarian cysts are estimated to occur spontaneously in approximately 1% to 5% of the normal female population.

Baclofen injection (intrathecal), USP is a clear, colorless, sterile, pyrogen-free, isotonic solution consisting of the active ingredient, Baclofen USP, and the excipients Sodium Chloride USP and Water for Injection USP in single-dose clear glass vials. Baclofen Injection (Intrathecal) is packaged in single-dose vials containing 10 mg/20 mL (500 mcg/mL) or 40 mg/20 mL (2000 mcg/mL) supplied as follows: One vial containing 10 mg/20 mL (500 mcg/mL) (NDC 70511-122-10). One vial containing 40 mg/20 mL (2000 mcg/mL) (NDC 70511-124-10). Does not require refrigeration. Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F)[See USP Controlled Room Temperature] Do not freeze. Do not heat sterilize

The precise mechanism of action of baclofen as a muscle relaxant and antispasticity agent is not fully understood. Baclofen inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possibly by decreasing excitatory neurotransmitter release from primary afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect. Baclofen is a structural analog of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and may exert its effects by stimulation of the GABAB receptor subtype. Baclofen injection (intrathecal) when introduced directly into the intrathecal space permits effective CSF concentrations to be achieved with resultant plasma concentrations 100 times less than those occurring with oral administration. In people, as well as in animals, baclofen has been shown to have general CNS depressant properties as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression. Pharmacodynamics of Baclofen Injection (Intrathecal):   Intrathecal Bolus: Adult Patients: The onset of action is generally one-half hour to one hour after an intrathecal bolus. Peak spasmolytic effect is seen at approximately four hours after dosing and effects may last four to eight hours. Onset, peak response, and duration of action may vary with individual patients depending on the dose and severity of symptoms. Pediatric Patients: The onset, peak response and duration of action is similar to those seen in adult patients. Continuous Infusion: Baclofen injection (intrathecal)’s antispastic action is first seen at 6 to 8 hours after initiation of continuous infusion. Maximum activity is observed in 24 to 48 hours. Continuous Infusion: No additional information is available for pediatric patients. Pharmacokinetics of Baclofen Injection (Intrathecal): The pharmacokinetics of CSF clearance of baclofen injection (intrathecal) calculated from intrathecal bolus or continuous infusion studies approximates CSF turnover, suggesting elimination is by bulk-flow removal of CSF. Intrathecal Bolus: After a bolus lumbar injection of 50 or 100 mcg baclofen injection (intrathecal) in seven patients, the average CSF elimination half-life was 1.51 hours over the first four hours and the average CSF clearance was approximately 30 mL/hour. Continuous Infusion: The mean CSF clearance for baclofen injection (intrathecal) was approximately 30 mL/hour in a study involving ten patients on continuous intrathecal infusion. Concurrent plasma concentrations of baclofen during intrathecal administration are expected to be low (0­ to 5 ng/mL). Limited pharmacokinetic data suggest that a lumbar-cisternal concentration gradient of about 4:1 is established along the neuroaxis during baclofen infusion. This is based upon simultaneous CSF sampling via cisternal and lumbar tap in 5 patients receiving continuous baclofen infusion at the lumbar level at doses associated with therapeutic efficacy; the interpatient variability was great. The gradient was not altered by position. Six pediatric patients (age 8 to 18 years) receiving continuous intrathecal baclofen infusion at doses of 77 to 400 mcg/day had plasma baclofen levels near or below 10 ng/mL.

NDC 70511-122-20 Baclofen Injection (Intrathecal), USP 10 mg per 20 mL (500 mcg per mL) Sterile Solution for Intrathecal Injection 20 mL Single-Dose Vial Discard unused portion Rx only NDC 70511-122-20 Baclofen Injection (Intrathecal), USP 10 mg per 20 mL (500 mcg per mL) Rx only Sterile Solution for Intrathecal Injection Only Discard unused portion Contains one 20 mL Single-Dose Vial vial-label-500mcg carton-500mcg