About the Therapy Intrathecal Baclofen Therapy with Lioresal® Intrathecal (baclofen injection)

FOR THE MANAGEMENT OF SEVERE SPASTICITY

ITB Therapy with Lioresal® Intrathecal (baclofen injection) for the management of severe spasticity uses an implantable infusion system to deliver precise amounts of Lioresal® Intrathecal (baclofen injection) directly to the intrathecal space via a surgically implanted infusion pump and catheter.

OVERVIEW OF SPASTICITY

Spasticity is an abnormal increase in muscle tone caused by injury of upper motor neuron pathways regulating muscles. Injury or disease of the central nervous system may cause spasticity. Spasticity may be a result of multiple sclerosis (MS), cerebral palsy (CP), stroke, brain injury, or spinal cord injury.

The consensus opinion of one expert panel defined spasticity as disordered sensori-motor control, resulting from upper motor neuro lesion, presenting intermittent or sustained involuntary activation of muscles.1

Severe spasticity can have a distressing effect on function, comfort, and care giving. It may result in musculoskeletal complications, incoordination, loss of function, pain, and permanent muscle shortening or contracture.

Treating severe spasticity may:

  • Improve gait, hygiene, activities of daily living, and ease of care
  • Decrease spasm frequency, pain, and fatigue
  • Promote tone reduction, increased range of motion, and joint position
  • Increase patient mobility
  • Complement other treatments, such as physical therapy, occupational therapy, and speech therapy

For patients with severe spasticity, enhancing their mobility, self-care abilities, and independence are significant achievements. To reach these milestones, effective therapy is necessary. Spasticity can be treated separately from the patient's primary underlying condition.

It can be difficult to effectively control severe spasticity. While physical rehabilitation and oral pharmacologic treatments work for many patients, some patients may not experience enough relief using these treatments alone. In addition, some patients encounter intolerable side effects from systemic medications. Patients with spasticity of spinal origin who are unresponsive to oral baclofen or who experience intolerable central nervous system (CNS) side effects from oral medications may benefit from ITB Therapy. ITB Therapy can significantly decrease severe spasticity2-10 and spasms.3, 8-10  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.

A patient should not receive ITB Therapy if the patient has an active infection, is hypersensitive to baclofen, has a body too small for an implantable pump, requires a pump implant deeper than 2.5 cm, or in the presence of spinal anomalies.

ITB THERAPY AS A TREATMENT OPTION

The intrathecal baclofen therapy system consists of a programmable pump, an intrathecal catheter, and an external programmer. The pump is surgically implanted in the patient's abdominal area, the catheter tip is placed in the intrathecal space, and the catheter is connected to the pump. Once implanted, the pump and catheter deliver Lioresal® Intrathecal (baclofen injection) directly to the patient's spinal fluid, where it can act directly in the spinal fluid. The Medtronic SynchroMed™ II infusion pump used for ITB Therapy can be noninvasively programmed to deliver a range of infusion rates, in a variety of dosing patterns.

ITB Therapy delivers baclofen directly into the intrathecal space, thereby bypassing the blood-brain barrier. As a result, only a fraction of the oral dose is needed to produce efficacy while minimizing systemic side effects.11

Three features of ITB Therapy are particularly desirable and important to most patients:

  • Control of Spasticity and Flexible Dosing Patterns — Use of a programmable infusion system for ITB Therapy permits clinicians to titrate dosage, providing graduated control of spasticity that not only meets the needs of individual patients at the time of implant, but that also can be adjusted whenever a change in dose is clinically indicated. It also enables physicians to deliver the drug on a variable schedule, e.g., providing greater spasticity control at night than during the day.12
  • Effective Treatment for Upper and Lower Extremity Spasticity — ITB Therapy reduces upper and lower extremity spasticity.4, 5, 13 Treatment may reduce spasticity and promote function among quadriplegic/tetraplegic as well as diplegic patients.5, 14-15
  • Reversibility of Treatment — Patients and their families can be reluctant to undergo destructive neurosurgical procedures. ITB Therapy may be considered an alternative to such procedures.

The most frequent drug adverse events vary by indication but include: hypotonia (34.7%), somnolence (20.9%), headache (10.7%), convulsion (10.0%), dizziness (8.0%), urinary retention (8.0%), nausea (7.3%), and paresthesia (6.7%). Pump system component failures leading to pump stall, or dosing/programming errors may result in clinically significant overdose or withdrawal. Acute massive overdose may result in coma and may be life-threatening.

HOW ITB THERAPY HELPS TREAT SEVERE SPASTICITY

Baclofen is a structural analog of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and may exert its effects by stimulation of the GABABreceptor subtype. However, 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.11

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.11

1

Pandyan AD, Gregoric M, Barnes MP et al. Spasticity: clinical perceptions, neurological realities and meaningful measurement. Disabil Rehabil 2005;27:2–6.

2

Francisco GC, Boake C. Improvement in walking speed in poststroke spastic hemiplegia after intrathecal baclofen therapy: a preliminary study. Arch Phys Med Rehabil. 2003;84(8):1194-1199.

3

Meythaler JM, Guin-Refroe S, Brunner RC, Hadley MN. Intrathecal baclofen for spastic hypertonia from stroke. Stroke. 2001;32(9):2099-2109.

4

Ivanhoe CB, Francisco GE, McGuire JR, Subramanian T, Grissom SP. Intrathecal baclofen management of poststroke spastic hypertonia: implications for function and quality of life. Arch Phys Med Rehabil. 2006;87(11):1509–1515.

5

Gilmartin R. Intrathecal baclofen for management of spastic cerebral palsy: multicenter trial. J Child Neurol. 2000;15(2):71-77.

6

Penn RD. Intrathecal baclofen for spasticity of spinal origin: seven years of experience. J Neurosurg. 1992;77(2):236-240.

7

Albright AL, Gilmartin R, Swift D, Krach LE, Ivanhoe CB, McLaughlin JF. Long-term intrathecal baclofen therapy for severe spasticity of cerebral origin. J Neurosurg. 2003;98(2):291-295.

8

Coffey RJ, Cahill D, Steers W. Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg. 1993;78(6):226-232.

9

Ordia JI, Fischer E, Adamski E, Chagnon KG, Spatz EL. Continuous intrathecal baclofen infusion by a programmable pump in 131 consecutive patients with severe spasticity of spinal origin. Neuromodulation. 2002;5(1):16-24.

10

Becker R, Alberti O, Bauer BL. Continuous intrathecal baclofen infusion in severe spasticity after traumatic or hypoxic brain injury. J Neurol 1997; 224(3): 160-166

11

Lioresal® Intrathecal (baclofen injection) Drug Prescribing Information.

12

Natale M, Mirone G, Rotondo M, Moraci A. Intrathecal baclofen therapy for severe spasticity: Analysis on a series of 112 consecutive patients and future prospectives. Clin Neurol Neurosurg. 2012;114:321-325.

13

Guillaume D, Van Havenbergh A, Vloeberghs M, Vidal J, Roeste G. A clinical study of intrathecal baclofen using a programmable pump for intractable spasticity. Arch Phys Med Rehabil. 2005;86:2165-2171.

14

Hoving MA, van Raak EP, Spincemaille GH, Palmans LJ, Becher JG, Vles JS. Efficacy of intrathecal baclofen therapy in children with intractable spastic cerebral palsy: a randomised controlled trial. Eur J Paediatr Neurol. May 2009;13(3):240-246.

15

Shilt JS, Reeves S, Lai LP, et al. The outcome of intrathecal baclofen treatment on spastic diplegia: Preliminary results with a minimum of two year follow up. J Ped Rehab Med. 2008;255-61.


Lioresal® Intrathecal
(baclofen injection)

Important Safety Information

Indications and Usage

  • Lioresal® Intrathecal (baclofen injection) is a muscle relaxant and antispastic that is indicated for use in the management of severe spasticity of cerebral or spinal origin.
  • Lioresal® 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 Lioresal® Intrathecal into the intrathecal space.
  • For patients with spasticity of spinal origin, Lioresal® 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.
  • Prior to implantation of a device for chronic intrathecal infusion of Lioresal® Intrathecal, patients must show a response to Lioresal® Intrathecal in a screening trial. Please review the dosing and administration section of the Lioresal® Intrathecal prescribing information for further details.
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 postimplant clinician and patient information (see WARNINGS).

Contraindications

  • Hypersensitivity to baclofen
  • Lioresal® Intrathecal is not recommended for intravenous, intramuscular, subcutaneous or epidural administration.

Select Warnings and Precautions

  • It is mandatory that all patients, caregivers, and treating physicians receive adequate information regarding the risks of the mode of treatment. Instruction 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 postimplant clinician and patient information (see WARNINGS). should be given on signs and symptoms of overdose, procedures to be followed in the event of an overdose, and proper home care of the pump and insertion site.
  • Due to the possibility of life-threatening CNS depression, cardiovascular collapse, and/or respiratory failure, physicians must be adequately trained and educated in chronic intrathecal infusion therapy.
  • Patients should be infection-free prior to both a screening trial and a pump implantation. The presence of infection may interfere with an assessment of the patient’s response to bolus Lioresal® Intrathecal (baclofen injection), increase the risk of surgical complications and complicate dosing.
  • Reservoir refilling must be performed by fully trained and qualified personnel following the directions provided by the pump manufacturer. Extreme caution must be used when filling an FDA approved implantable pump, following strict aseptic technique and ensuring refill directly into the reservoir and not the catheter access port.
  • 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 Lioresal® Intrathecal infusion.
  • Following pump implantation, and for each adjustment of the dosing rate of the pump and/or concentration of Lioresal® Intrathecal, the patient should be monitored closely until it is certain the patient’s response to the infusion is acceptable and reasonably stable.
  • Early symptoms of baclofen withdrawal may include return of baseline spasticity, pruritus, hypotension and paresthesias.
  • Priapism may develop or recur if treatment with intrathecal baclofen is interrupted.
  • Signs of overdose may appear suddenly or insidiously, and a 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 pump reservoir.
  • Delivery of more drug volume than the programmed rate (overinfusion) can result in unexpected overdose, or withdrawal caused by early emptying of the pump reservoir. Refer to the manufacturer's pump manual and instructions for refilling the reservoir.
  • Except in overdose related emergencies, the dose of Lioresal® Intrathecal should ordinarily be reduced slowly if the drug is discontinued for any reason.

Adverse Reactions

Common Adverse Reactions

  • The most frequent drug adverse events vary by indication but include: hypotonia (34.7%), somnolence (20.9%), headache (10.7%), convulsion (10.0%), dizziness (8.0%), urinary retention (8.0%), nausea (7.3%), and paresthesia (6.7%). Dosing and programming errors may result in clinically significant overdose or withdrawal. Acute massive overdose may result in coma and may be life threatening.
  • Drowsiness has been reported in patients on Lioresal® 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 Lioresal® Intrathecal may be additive to those of alcohol and other CNS depressants.

Serious Adverse Reactions

  • Seizures have been reported during overdose and with withdrawal from Lioresal® Intrathecal (baclofen injection) as well as in patients maintained on therapeutic doses of Lioresal® Intrathecal.
  • Fatalities have been reported with Lioresal® Intrathecal use.

Postmarketing Experience

  • The following adverse events have been reported during post-approval use of Lioresal® Intrathecal.
    • Musculoskeletal – The onset of scoliosis or worsening of a pre-existing scoliosis has been reported.
    • Urogenital – Sexual dysfunction in men and women including decreased libido and orgasm dysfunction have been reported.

Use in Specific Populations

  • There are no adequate and well controlled studies in pregnant women. Lioresal® Intrathecal should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Nursing mothers should exercise caution, as oral baclofen has been shown to pass into milk at therapeutic doses.
  • Safety and effectiveness in pediatric patients below the age of 4 have not been established.
  • Patients suffering from psychotic disorders, schizophrenia, or confusional states should be treated cautiously with Lioresal® Intrathecal and kept under careful surveillance.
  • Lioresal® Intrathecal should be given with caution in patients with impaired renal function. Dose reduction may be necessary.
  • Lioresal® Intrathecal should be used with caution in patients with a history of autonomic dysreflexia.

For more information, including BOX WARNING, refer to Lioresal® Intrathecal (baclofen injection) prescribing information, located at www.lioresal.com/prescribinginformation

Rev. 06/2019