CLINICAL STUDY HIGHLIGHTS Intrathecal Baclofen Therapy with Lioresal® Intrathecal (baclofen injection)

PROVEN SAFETY AND EFFICACY PROFILE

ITB Therapy with Lioresal® Intrathecal (baclofen injection) has been proven through clinical studies to demonstrate safety and efficacy of screening and during long-term therapy.

SCREENING TEST RESULTS

  • 94% of patients with spasticity of cerebral origin demonstrated a positive response to the screening test for ITB Therapy in one study.1
  • 97% of patients with spasticity of spinal origin demonstrated a positive response to the screening test for ITB Therapy in one clinical study.2
  • 87% of physicians rated their overall satisfaction for each patient's outcomes as good or very good in one clinical study, despite the occurrence of complications.3

LONG-TERM EFFECTIVENESS

Two clinical studies have demonstrated that severe spasticity of spinal origin responds to long-term ITB Therapy.2,4 Long-term control of severe spasticity was achieved in most patients in the studies. Complications and side effects were reported in both studies. The most common device-related complications were catheter kinks, dislodgments, and disconnections. The most common drug-related side effects were drowsiness, dizziness, blurred vision, slurred speech, hypotension, depression, and seizures.

Long-term effectiveness in spasticity of cerebral origin has been demonstrated (median of 67 months) with ITB Therapy; adverse effects experienced in the study were usually managed by dose adjustments. The most commonly reported drug-related adverse effects were hypotonia (25%), somnolence (19%), seizures (13%), and headache (2%).5

A statistically significant improvement was demonstrated with ITB Therapy in muscle tone, function, and quality of life among stroke survivors. Adverse events in this study included accidental injury (11%), somnolence (10%), dizziness (10%), hypotonia (8%), headache (5%), constipation (5%), pain (5%), urinary tract infection (5%), and hypertonia (5%).6

Subjective reports from caregivers indicate a reduction in use of oral medication for spasticity,7 and improvements in comfort, function, and/or ease of care7,8 during ITB Therapy.

1

Gilmartin R, Bruce D, Storrs BB, et al. Intrathecal baclofen for management of spastic cerebral palsy: multicenter trial. J Child Neurol. 2000;15:71-77.

2

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

3

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.

4

Coffey RJ, Cahill D, Steers W, et al. Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multi-center study. J Neurosurg. 1993;78:226-232.

5

Albright AL, Gilmartin R, Swift D, et al. Long-term intrathecal baclofen therapy for severe spasticity of cerebral origin. J Neurosurg. 2003;98:291-295.

6

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;87:1509-1515.

7

Campbell, WM, et al. Long-term safety and efficacy of continuous intrathecal baclofen. Dev Med Child Neurol. 2002;44:660-665.

8

Middel B, et al. Effect of intrathecal baclofen delivered by an implanted programmable pump on health related quality of life in patients with severe spasticity. J Neurol Neurosurg Psychiatry. 1997;63:204-209.

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 BOXED WARNING, refer to Lioresal® Intrathecal (baclofen injection) prescribing information, located at lioresal.com/prescribinginformation.

Rev. 06/2019