Targeted Delivery for Effective Control

Home Lioresal® Intrathecal Home Page Dosing and Administration Targeted Delivery for Effective Control

Because ITB therapy delivers baclofen directly to the site of action, it can provide more accurate and individualized dosing with lower baclofen dosages.^1,2 With ITB Therapy℠ with Lioresal^® Intrathecal (baclofen injection), there is 100 times less medication is in the blood compared to oral baclofen at recommended dosages.¹ Specific concentrations of baclofen needed depend on the total daily dose required to treat severe spasticity. In clinical studies in patients with spinal cord injury, maintenance continuous infusion dosages have ranged from 12 to 2003 mcg/L, with most patients maintained on 300 to 800 mcg/L. Similarly, for patients with cerebral palsy, maintenance continuous infusion dosages have ranged from 22 to 1900 mcg/L, with most patients maintained on 90 to 703 mcg/L. In these patients, plasma concentrations are expected to be 0 to 5 mcg/L.¹

Stable dosages can be maintained long-term. In a cross-sectional survey of patients receiving ITB therapy or oral baclofen, the mean change in ITB dosages ranged from 3% to 5% over 3 years, whereas the mean change in oral dosages ranged from 9% to 21%.³

Importantly, even with a lower dose, spasticity is significantly less frequent and less severe with ITB therapy. With bolus dosing of baclofen, ITB therapy resulted in an improvement in Modified Ashworth Scale (MAS) scores within 1 hour, with maximal effect generally occurring 4 hours after dosing. This effect typically lasts 4 to 8 hours. With continuous infusion, antispastic activity is first seen at 6 to 8 hours after initiation and lasts 24 to 48 hours. Mean spasm frequency and severity scores with ITB therapy indicated spasms only occurred with stimulation and were mild in severity. In contrast, with oral baclofen, scores indicated infrequent but full spasms that occurred less than once per hour and were moderate in severity.^1,3

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.

Lioresal^® Intrathecal (baclofen injection) for intrathecal injection [prescribing information]. Saol Therapeutics, Roswell, Georgia; January 2019.
Kemstro^TM (baclofen orally disintegrating tablets) for oral use [prescribing information]. Milwaukee, WI: Schwarz Pharma; Revised October 2003.
McCormick ZL, Chu SK, Binler D, et al. Intrathecal versus oral baclofen: a matched cohort study of spasticity, pain, sleep, fatigue, and quality of life. PM R. 2016;8(6):553-562.
Heetla HW, Proost JH, Molmans BH, Staal MJ, van Laar T. A pharmacokinetic-pharmacodynamic model for intrathecal baclofen in patients with severe spasticity. Br J Clin Pharmacol. 2016;81(1):101-112.

Important Safety Information for Lioresal^® Intrathecal (baclofen injection)

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).

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.

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.

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 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, 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.

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

Serious Adverse Reactions

Seizures have been reported during overdose and with withdrawal from Lioresal^® Intrathecal 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.

Lioresal Intrathecal (baclofen injection)

Difference in Dosages in a 3-Year Study of ITB Therapy vs Oral Baclofen³

MAS Scores After Continuous Dosing of Oral Baclofen and Bolus Dosing with ITB Therapy⁴

Frequency and Severity of Spasms^a in Patients With Spinal Cord Injury, Cerebral Palsy, and Stroke after 3 Years of Oral Baclofen or ITB Therapy⁴

Important Safety Information for Lioresal^® Intrathecal (baclofen injection)

Important Safety Information for Lioresal^® Intrathecal (baclofen injection)

Indications and Usage

Contraindications

Select Warnings and Precautions

Adverse Reactions

Use in Specific Populations

Targeted Delivery for Effective Control

Difference in Dosages in a 3-Year Study of ITB Therapy vs Oral Baclofen3

MAS Scores After Continuous Dosing of Oral Baclofen and Bolus Dosing with ITB Therapy4

Frequency and Severity of Spasmsa in Patients With Spinal Cord Injury, Cerebral Palsy, and Stroke after 3 Years of Oral Baclofen or ITB Therapy4

Important Safety Information for Lioresal® Intrathecal (baclofen injection)

Indications and Usage

Contraindications

Select Warnings and Precautions

Adverse Reactions

Use in Specific Populations

Difference in Dosages in a 3-Year Study of ITB Therapy vs Oral Baclofen³

MAS Scores After Continuous Dosing of Oral Baclofen and Bolus Dosing with ITB Therapy⁴

Frequency and Severity of Spasms^a in Patients With Spinal Cord Injury, Cerebral Palsy, and Stroke after 3 Years of Oral Baclofen or ITB Therapy⁴

Important Safety Information for Lioresal^® Intrathecal (baclofen injection)