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) ] . Baclofen injection is a gamma-aminobutyric acid (GABA) ergic agonist indicated for use in the management of severe spasticity of cerebral or spinal origin in adult and pediatric patients age 4 years and above. ( 1 ) Baclofen injection should be reserved for patients unresponsive to oral baclofen therapy, or those who experience intolerable central nervous system side effects at effective doses.
( 1 ) Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump. ( 1 ) Spasticity due to traumatic brain injury: wait at least one year after injury before considering baclofen injection therapy. ( 1 )
Contraindications
Baclofen injection is contraindicated in patients with a hypersensitivity to baclofen. Do not use baclofen injection for intravenous, intramuscular, subcutaneous or epidural administration. Hypersensitivity to baclofen ( 4 ) Do not use baclofen injection for intravenous, intramuscular, subcutaneous or epidural administration. (4)
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Do not directly inject baclofen injection into the pump catheter access port, as this may cause a life-threatening overdose. ( 5.1 ) Potential for contamination due to non-sterile external surface of prefilled syringe. ( 5.2 ) Potentially life-threatening CNS depression, cardiovascular collapse, and/or respiratory failure; Resuscitative equipment and trained staff must be available during screening, dose titration, and refills ( 5.3 ) Overdose may cause drowsiness, lightheadedness, dizziness, somnolence, respiratory depression, seizures, rostral progression of hypotonia and loss of consciousness progressing to coma.
( 5.4 ) Possible exacerbation of psychotic disorders, schizophrenia or confusional states ( 5.6 )
5.1Risk of Life-Threatening Overdose During Pump Refills
Use extreme caution when filling the Medtronic SynchroMed ® II Programmable Pump which is 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. Reservoir refilling must be performed by fully trained and qualified personnel following the directions provided by the pump manufacturer.
Carefully calculate refill intervals 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.
5.2 Potential for Contamination due to Non-sterile External Surface of Prefilled Syringe Although the drug solution and pathway in the baclofen injection prefilled syringes are sterile, the external surface of the prefilled syringes (all strengths, including the 50 mcg/mL strength) are non-sterile. This has the potential to lead to contamination and consequent adverse reactions. The use of baclofen injection prefilled syringe in an aseptic setting (e.g., operating room) to fill sterile intrathecal pumps prior to implantation in patients is not recommended, unless the external surface of the prefilled syringe is treated to ensure sterility.
Baclofen injection supplied in vials may be used with conventional aseptic technique to fill intrathecal pumps prior to implantation. Procedures should also be put in place while refilling implantable intrathecal pumps in an outpatient setting to avoid contamination of sterile surfaces through contact with the non-sterile exterior of the baclofen injection prefilled syringe.
5.3Prescriber, Caregiver and Patient Training and Screening Procedure/Post- Implantation Environment
Baclofen injection is for use in single bolus intrathecal injections (via a catheter placed in the lumbar intrathecal space or injection by lumbar puncture) and in the implantable Medtronic SynchroMed® II Programmable Pump or other pumps labeled for intrathecal administration of baclofen injection. Because of the possibility of potentially life-threatening CNS depression, cardiovascular collapse, and/or respiratory failure, physicians must be adequately trained and educated in chronic intrathecal infusion therapy.
The pump system should not be implanted until the patient's response to bolus baclofen injection injection is adequately evaluated. Evaluation (consisting of a screening procedure) requires that baclofen injection be administered into the intrathecal space via a catheter or lumbar puncture [see Dosage and Administration (2.2) ] . Because of the risks associated with the screening procedure and the adjustment of dosage following pump implantation, these phases must be conducted in a medically supervised and adequately equipped environment following the instructions outlined in the Dosage and Administration section [see Dosage and Administration ( 2.2 and 2.5 )] .
Resuscitative equipment should be available. Following surgical implantation of the pump, particularly during the initial phases of pump use, the patient should be monitored closely until it is certain that the patient's response to the infusion is acceptable and reasonably stable. On each occasion that the dosing rate of the pump and/or the concentration of baclofen injection in the reservoir is adjusted, close medical monitoring is required until it is certain that the patient's response to the infusion is acceptable and reasonably stable.
It is mandatory that the patient, all patient caregivers, and the physicians responsible for the patient receive adequate information regarding the risks of this mode of treatment. All medical personnel and caregivers should be instructed in 1) the signs and symptoms of overdose, 2) procedures to be followed in the event of overdose and 3) proper home care of the pump and insertion site.
5.4Overdose Signs
of overdose may appear suddenly or insidiously. Acute massive overdose may present as coma. Less sudden and/or less severe forms of overdose may present with signs of drowsiness, lightheadedness, dizziness, somnolence, respiratory depression, seizures, rostral progression of hypotonia and loss of consciousness progressing to coma. Should overdose appear likely, the patient should be taken immediately to a hospital for assessment and emptying of the pump reservoir.
In cases reported to date, overdose has generally been related to pump malfunction or dosing error [see Overdosage (10) ] . Extreme caution must be used when filling the implantable pump. Medtronic SynchroMed® II Programmable Pump should only be refilled through the reservoir refill septum. The Medtronic SynchroMed® II Programmable Pump is also equipped with a catheter access port that allows direct access to the intrathecal catheter.
Direct injection into this catheter access port may cause a life-threatening overdose.
5.5Withdrawal
Abrupt withdrawal of intrathecal baclofen, regardless of the cause, has resulted in sequelae that included high fever, altered mental status, exaggerated rebound spasticity and muscle rigidity that in rare cases progressed to rhabdomyolysis, multiple organ- system failure, and death. In the first 9 years of post-marketing experience, 27 cases of withdrawal temporally related to the cessation of baclofen therapy were reported; six patients died.
In most cases, symptoms of withdrawal appeared within hours to a few days following interruption of baclofen therapy. Common reasons for abrupt interruption of intrathecal baclofen therapy included malfunction of the catheter (especially disconnection), low volume in the pump reservoir, and end of pump battery life; human error may have played a causal or contributing role in some cases. Cases of intrathecal mass at the tip of the implanted catheter leading to withdrawal symptoms have also been reported, most of them involving pharmacy compounded analgesic admixtures [see Warnings and Precautions (5.10) ] .
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. All patients receiving intrathecal baclofen therapy are potentially at risk for withdrawal.
Early symptoms of baclofen withdrawal may include return of baseline spasticity, pruritus, hypotension, and paresthesias. Some clinical characteristics of the advanced intrathecal baclofen withdrawal syndrome may resemble autonomic dysreflexia, infection (sepsis), malignant hyperthermia, neuroleptic-malignant syndrome, or other conditions associated with a hypermetabolic state or widespread rhabdomyolysis. Rapid, accurate diagnosis and treatment in an emergency-room or intensive-care setting are important in order to prevent the potentially life-threatening centra
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Interactions
There is inadequate systematic experience with the use of intrathecal baclofen in combination with other medications to predict specific drug-drug interactions. Interactions attributed to the combined use of baclofen injection and epidural morphine include hypotension and dyspnea. Combined use with morphine: hypotension and dyspnea
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
There are no adequate data on the developmental risk associated with the use of baclofen injection in pregnant women. In animal studies, oral administration of baclofen to pregnant rats produced an increase in fetal malformations (see Data) . There are no animal data on developmental risk associated with baclofen administered via continuous intrathecal infusion. The background risk of major birth defects and miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Baclofen given orally to pregnant rats has been shown to increase the incidence of omphaloceles (ventral hernias) in fetuses at a dose associated with maternal toxicity. This abnormality was not seen in mice or rabbits.
Adverse reactions
The most common adverse reactions in patients with spasticity of spinal origin were somnolence, dizziness, nausea, hypotension, headache, convulsions and hypotonia. ( 6.1 ) The most common adverse reactions in patients with spasticity of cerebral origin were agitation, constipation, somnolence, leukocytosis, chills, urinary retention and hypotonia. ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Nexus Pharmaceuticals at 1-855-642-2594 or email: safety.nexuspharma@lambda-cro.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Spasticity of Spinal Cord Origin Most Common Adverse Reactions in Patients with Spasticity of Spinal Origin In pre- and post-marketing clinical trials, the most common adverse reactions associated with use of intrathecal baclofen which were not seen at an equivalent incidence among placebo-treated patients were: somnolence, dizziness, nausea, hypotension, headache, convulsions and hypotonia. Adverse Reactions Associated with Discontinuation of Treatment 8/474 patients with spasticity of spinal cord origin receiving long term infusion of intrathecal baclofen in pre- and post-marketing clinical studies in the U.S. discontinued treatment due to adverse reactions.
These include: pump pocket infections (3), meningitis (2), wound dehiscence (1), gynecological fibroids (1) and pump overpressurization (1) with unknown, if any, sequela. Eleven patients who developed coma secondary to overdose had their treatment temporarily suspended, but all were subsequently re-started and were not, therefore, considered to be true discontinuations. Fatalities - [see Warnings and Precautions (5.6)] .
Incidence in Controlled Trials Experience with intrathecal baclofen obtained in parallel, placebo-controlled, randomized studies provides only a limited basis for estimating the incidence of adverse reactions because the studies were of very brief duration (up to three days of infusion) and involved only a total of 63 patients. The following events occurred among the 31 patients receiving intrathecal baclofen in two randomized, placebo-controlled trials: hypotension (2), dizziness (2), headache (2), dyspnea (1).
No adverse reactions were reported among the 32 patients receiving placebo in these studies. Events Observed during the Pre- and Post-marketing Evaluation of Intrathecal Baclofen Adverse events associated with the use of intrathecal baclofen reflect experience gained with 576 patients followed prospectively in the United States. They received intrathecal baclofen for periods of one day (screening) (N=576) to over eight years (maintenance) (N=10).
The usual screening bolus dose administered prior to pump implantation in these studies was typically 50 mcg. The maintenance dose ranged from 12 mcg to 2,003 mcg per day. Because of the open, uncontrolled nature of the experience, a causal linkage between events observed and the administration of intrathecal baclofen cannot be reliably assessed in many cases and many of the adverse reactions reported are known to occur in association with the underlying conditions being treated.
Nonetheless, many of the more commonly reported reactions — hypotonia, somnolence, dizziness, paresthesia, nausea/vomiting and headache — appear clearly drug-related. Adverse experiences reported during all U.S. studies (both controlled and uncontrolled) are shown in Table 1. Eight of 474 patients who received chronic infusion via implanted pumps had adverse experiences which led to a discontinuation of long term treatment in the pre- and post-marketing studies.
Table 1: Most Common (≥1%) Adverse Reactions in Patients with Spasticity of Spinal Origin in Prospectively Monitored Clinical Trials Adverse Reaction Percent N=576 Screening* Percent N=474 Titration† Percent N=430 Maintenance ‡ Hypotonia 5.4 13.5
25.3 Somnolence 5.7 5.9
20.9 Dizziness 1.7 1.9
7.9 Paresthesia 2.4 2.1
6.7 Nausea and Vomiting 1.6 2.3
5.6 Headache 1.6 2.5
5.1 Constipation 0.2 1.5
5.1 Convulsion 0.5 1.3
4.7 Urinary Retention 0.7 1.7
1.9 Dry Mouth 0.2 0.4
3.3 Accidental Injury 0.0 0.2
3.5 Asthenia 0.7 1.3
1.4 Confusion 0.5 0.6
2.3 Death 0.2 0.4
3.0 Pain 0.0 0.6
3.0 Speech Disorder 0.0 0.2
3.5 Hypotension 1.0 0.2
1.9 Ambylopia 0.5 0.2
2.3 Diarrhea 0.0 0.8
2.3 Hypoventilation 0.2 0.8
2.1 Coma 0.0 1.5
0.9 Impotence 0.2 0.4
1.6 Peripheral Edema 0.0 0.0
2.3 Urinary Incontinence 0.0 0.8
1.4 Insomnia 0.0 0.4
1.6 Anxiety 0.2 0.4
0.9 Depression 0.0 0.0
1.6 Dyspnea 0.3 0.0
1.2 Fever 0.5 0.2
0.7 Pneumonia 0.2 0.2
1.2 Urinary Frequency 0.0 0.6
0.9 Urticaria 0.2 0.2
1.2 Anorexia 0.0 0.4
0.9 Diplopia 0.0 0.4
0.9 Dysautonomia 0.2 0.2
0.9 Hallucinations 0.3 0.4
0.5Hypertension 0.2 0.6
0.5 * Following administration of test bolus † Two month period following implant ‡ Beyond two months following implant N=Total number of patients entering each period %=% of patients evaluated In addition to the more common (1% or more) adverse reactions reported in the prospectively followed 576 domestic patients in pre- and post-marketing studies, experience from an additional 194 patients exposed to intrathecal baclofen from foreign studies has been reported.
The following adverse reactions, not described in the table, and arranged in decreasing order of frequency, and classified by body system, were reported: Nervous System: Abnormal gait, thinking abnormal, tremor, amnesia, twitching, vasodilatation, cerebrovascular accident, nystagmus, personality disorder, psychotic depression, cerebral ischemia, emotional lability, euphoria, hypertonia, ileus, drug dependence, incoordination, paranoid reaction and ptosis.
Digestive System: Flatulence, dysphagia, dyspepsia and gastroenteritis. Cardiovascular: Postural hypotension, bradycardia, palpitations, syncope, arrhythmia ventricular, deep thrombophlebitis, pallor and tachycardia. Respiratory: Respiratory disorder, aspiration pneumonia, hyperventilation, pulmonary embolus and rhinitis. Urogenital: Hematuria and kidney failure. Skin and Appendages: Alopecia and sweating. Metabolic and Nutritional Disorders: Weight loss, albuminuria, dehydration and hyperglycemia.
Special Senses: Abnormal vision, abnormality of accommodation, photophobia, taste loss and tinnitus. Body as a Whole: Suicide, lack of drug effect, abdominal pain, hypothermia, neck rigidity, chest pain, chills, face edema, flu syndrome and overdose. Hemic and Lymphatic System: Anemia.
6.2Spasticity of Cerebral Origin Most Common Adverse Reactions
In pre-marketing clinical trials, the most common adverse reactions associated with use of intrathecal baclofen which were not seen at an equivalent incidence among placebo- treated patients included: agitation, constipation, somnolence, leukocytosis, chills, urinary retention and hypotonia. Adverse Reactions Associated with Discontinuation of Treatment Nine of 211 patients receiving intrathecal baclofen in pre-marketing clinical studies in the U.S. discontinued long-term infusion due to adverse reactions associated with intrathecal therapy.
The nine adverse reactions leading to discontinuation were: infection (3), CSF leaks (2), meningitis (2), drainage (1), and unmanageable trunk control (1). Fatalities Three deaths, none of which were attributed to intrathecal baclofen, were reported in patients in clinical trials involving patients with spasticity of cerebral origin. See Warnings on other deaths reported in spinal spasticity patients. Incidence in Controlled Trials Experience with intrathecal baclofen obtained in parallel, placebo-controlled, randomized studies provides only a limited basis for estimating the incidence of adverse reactions because the studies involved a total of 62 patients exposed to a single 50 mcg intrathecal bolus.
The following adverse reactions occurred among the 62 patients receiving intrathecal baclofen in two randomized, placebo-controlled trials involving cerebral palsy and head injury patients, respectively: agitation, constipation, somnolence, leukocytosis, nausea, vomiting, nystagm
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Composition
Active ingredients
BACLOFEN 2MG/ML
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
