Brand names: Gablofen, Lioresal
Drug class: GABA-derivative Skeletal Muscle Relaxants
VA class: MS200
Chemical name: 4-Amino-3-(4-chlorophenyl)-butanoic acid
Molecular formula: C₁₀H₁₂ClNO₂
CAS number: 1134-47-0

Medically reviewed by Drugs.com on Oct 5, 2023. Written by ASHP.

Introduction

Skeletal muscle relaxant and antispastic agent; a GABA derivative.

Uses for Baclofen

Spasticity

Oral management of spasticity and its sequelae secondary to severe chronic disorders such as multiple sclerosis and other types of spinal cord lesions. Not indicated for use in patients with rheumatic disorders. Efficacy not established in patients with stroke, cerebral palsy, or Parkinson’s disease; use not recommended in these patients.

Intrathecal management of severe spasticity of spinal cord origin in patients who do not tolerate or respond adequately to oral baclofen; considered an alternative to destructive neurosurgical procedures. Also, intrathecal management of intractable spasticity secondary to severe chronic disorders such as multiple sclerosis and other types of spinal diseases such as spinal ischemia, spinal tumor, transverse myelitis, cervical spondylosis, and degenerative myelopathy; designated an orphan drug by FDA for use in these conditions.

Intrathecal management of severe spasticity of cerebral origin, including cerebral palsy and acquired brain injury; considered an alternative to destructive neurosurgical procedures. Designated an orphan drug by FDA for management of spasticity in patients with cerebral palsy. Patients with spasticity secondary to traumatic brain injury should wait ≥1 year after the injury before considering long-term intrathecal baclofen therapy.

Baclofen Dosage and Administration

General

• Clinical goal is to maintain muscle tone as close to normal as possible and to minimize frequency and severity of spasms without inducing intolerable adverse effects. May be important to maintain some degree of muscle tone and allow occasional spasms to help support circulatory function, minimize risk of DVT occurrence, and optimize activities of daily living and ease of care.

• Individualize dosage according to patient’s requirements and response; use lowest dosage that produces optimum response.

• Some patients require 1–2 months of oral treatment for full benefit. If benefits are not evident after a reasonable trial period, discontinue therapy by slowly reducing daily dosage.

• Prior to implantation of pump for chronic intrathecal baclofen therapy, patient must exhibit positive response (clinically important decrease in muscle tone and/or frequency and/or severity of spasms over 4- to 8-hour observation period) to initial intrathecal test dose(s) (screening phase).

• In patients receiving intrathecal baclofen therapy, closely monitor patients in a fully equipped and staffed environment during initial test for responsiveness and dosage-titration period immediately following implantation of pump. Resuscitative equipment should be immediately available for use in case of life-threatening or intolerable adverse effects.

• Tolerance may develop during chronic intrathecal baclofen therapy. No firm recommendations regarding amelioration of tolerance; patients occasionally have been hospitalized and intrathecal baclofen dosage decreased gradually over 2- to 4-week period, during which baclofen was alternated with other methods of spasticity management. Sensitivity to baclofen may return after a few days, and continuous intrathecal baclofen therapy may be resumed at the previously effective initial dosage.

Administration

Administer orally or intrathecally.

Baclofen injection for intrathecal administration is not recommended or intended for IV, IM, sub-Q, or epidural administration.

Avoid abrupt discontinuance (because of risk of precipitating withdrawal). Reduce dosage slowly when discontinuing drug, except for serious adverse reactions. (See Warnings under Cautions.)

Oral Administration

Administer orally 3 times daily.

Intrathecal Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer test dose(s) during screening phase by direct intrathecal injection (via lumbar puncture or catheter) over ≥1 minute employing barbotage.

Administer maintenance regimen by continuous intrathecal infusion into a lumbar intrathecal space via an implantable controlled-infusion device (e.g., Medtronic SynchroMed pump).

Consult manufacturer’s labeling for specialized administration techniques.

Consult manual provided by manufacturer of implantable infusion device for specific instructions and precautions for programming pump and/or refilling reservoir. Various pumps (with different reservoir volumes) and refill kits are available; clinicians must be familiar with these products in order to select the appropriate refill kit for the particular pump in use.

Dilution

To prepare test doses for screening phase, use 1-mL ampuls containing 50 mcg of baclofen without further dilution. Ampuls are for single use only; discard any unused portion.

For maintenance therapy in patients receiving concentrations other than the commercially available strengths (i.e., 0.5 or 2 mg/mL), injection concentrate must be diluted with sterile, preservative-free 0.9% sodium chloride for injection.

Rate of Administration

Test dose(s): Direct intrathecal injection by barbotage over ≥1 minute.

Maintenance regimen: Continuous intrathecal infusion.

Dosage

Pediatric Patients

Spasticity

Oral

Children ≥12 Years of Age: Initially, 5 mg 3 times daily. Increase daily dosage by 15 mg (in 3 divided doses) at 3-day intervals (i.e., 5 mg 3 times daily for 3 days, then 10 mg 3 times daily for 3 days, then 15 mg 3 times daily for 3 days, then 20 mg 3 times daily for 3 days) until optimum effect is achieved.

Usual dosage in children ≥12 years of age is 40–80 mg daily.

Screening for Response to Intrathecal Baclofen in Severe Spasticity

Intrathecal

Administer test dose of 50 mcg (1 mL of 50-mcg/mL solution) into intrathecal space by barbotage over ≥1 minute; may consider an initial dose of 25 mcg in very small children.

If response observed at 4–8 hours after initial test dose is less than desired, administer a second test dose of 75 mcg (1.5 mL of a 50-mcg/mL solution) 24 hours after first test dose.

If response observed at 4–8 hours after the second test dose remains inadequate, administer a final test dose of 100 mcg (2 mL of a 50-mcg/mL solution) 24 hours after second test dose.

Patients not responding to 100-mcg test dose are not candidates for chronic intrathecal therapy.

Maintenance Therapy for Severe Spasticity

Intrathecal

Following establishment of responsiveness to intrathecal baclofen, administer initial daily dose over 24 hours.

Initial daily dose is twice the test dose that produced a positive response with a duration not >8 hours. If positive response to test dose persisted >8 hours, initial dose is the same as the test dose that produced a positive response.

Following the initial infusion dose in children with spasticity of spinal cord or cerebral origin, increase daily dosage slowly (by 5–15% increments at 24-hour intervals) until desired clinical response is achieved.

May need to adjust maintenance dosage often during initial months of therapy. During periodic pump refills, increase the 24-hour dose by up to 10–40% in patients with spasticity of spinal cord origin or up to 5–20% in those with spasticity of cerebral origin as necessary to maintain adequate control of symptoms. In patients who develop intolerable adverse effects, reduce the 24-hour dose by 10–20%.

Patients achieving relatively satisfactory relief may derive further benefit from more complex dosing schedules. For example, patients who commonly experience an exacerbation of spasticity that disrupts sleep may require a 20% increase in the hourly infusion rate (programmed to begin approximately 2 hours before the time of desired clinical benefit).

Maintenance dosage in most children >12 years of age: 300–800 mcg daily (range: 12–2003 mcg daily) in those with spasticity of spinal cord origin; 90–703 mcg daily (range: 22–1400 mcg daily) in those with spasticity of cerebral origin.

Average maintenance dosage in children <12 years of age: 274 mcg daily (range: 24–1199 mcg daily).

Adults

Spasticity

Oral

Initially, 5 mg 3 times daily. Increase daily dosage by 15 mg (in 3 divided doses) at 3-day intervals (i.e., 5 mg 3 times daily for 3 days, then 10 mg 3 times daily for 3 days, then 15 mg 3 times daily for 3 days, then 20 mg 3 times daily for 3 days) until optimum effect is achieved.

Usual dosage is 40–80 mg daily.

Screening for Response to Intrathecal Baclofen in Severe Spasticity

Intrathecal

Administer test dose of 50 mcg (1 mL of 50-mcg/mL solution) into intrathecal space by barbotage over ≥1 minute.

If response observed at 4–8 hours after initial test dose is less than desired, administer a second test dose of 75 mcg (1.5 mL of a 50-mcg/mL solution) 24 hours after first test dose.

If response observed at 4–8 hours after the second test dose remains inadequate, administer a final test dose of 100 mcg (2 mL of a 50-mcg/mL solution) 24 hours after second test dose.

Patients not responding to 100-mcg test dose are not candidates for chronic intrathecal therapy.

Maintenance Therapy for Severe Spasticity

Intrathecal

Following establishment of responsiveness to intrathecal baclofen, administer initial daily dose over 24 hours.

Initial daily dose is twice the test dose that produced a positive response with a duration not >8 hours. If positive response to test dose persisted >8 hours, initial dose is the same as the test dose that produced a positive response.

Following the initial infusion dose, increase daily dosage slowly until the desired clinical response is achieved: increase dosage by 10–30% increments at 24-hour intervals in adults with spasticity of spinal cord origin and by 5–15% increments at 24-hour intervals in adults with spasticity of cerebral origin.

May need to adjust maintenance dosage often during initial months of therapy. During periodic pump refills, increase the 24-hour dose by up to 10–40% in patients with spasticity of spinal cord origin or up to 5–20% in those with spasticity of cerebral origin as necessary to maintain adequate control of symptoms. In patients who develop intolerable adverse effects, reduce the 24-hour dose by 10–20%.

Patients achieving relatively satisfactory relief may derive further benefit from more complex dosing schedules. For example, patients who commonly experience an exacerbation of spasticity that disrupts sleep may require a 20% increase in the hourly infusion rate (programmed to begin approximately 2 hours before the time of desired clinical benefit).

Maintenance dosage in most patients: 300–800 mcg daily (range: 12–2003 mcg daily) in those with spasticity of spinal cord origin; 90–703 mcg daily (range: 22–1400 mcg daily) in those with spasticity of cerebral origin.

Prescribing Limits

Pediatric Patients

Spasticity

Oral

Some clinicians suggest that daily dosages up to 150 mg are well tolerated and provide additional therapeutic benefit in some patients; however, one manufacturer states that dosage should not exceed 80 mg daily (20 mg 4 times daily).

Intrathecal

Limited experience with maintenance dosages >1000 mcg daily.

Adults

Spasticity

Oral

Some clinicians suggest that daily dosages up to 150 mg are well tolerated and provide additional therapeutic benefit in some patients; however, one manufacturer states that dosage should not exceed 80 mg daily (20 mg 4 times daily).

Intrathecal

Limited experience with maintenance dosages >1000 mcg daily.

Special Populations

Renal Impairment

Reduction of oral or intrathecal dosage may be necessary.

Geriatric Patients

Increase oral dosage more gradually.

Patients with Psychiatric or Brain Disorders

Increase oral dosage more gradually.

Cautions for Baclofen

Contraindications

• Known hypersensitivity to baclofen or any ingredient in the formulation.

Warnings/Precautions

Warnings

Abrupt Withdrawal of Oral Therapy

Abrupt discontinuance of oral baclofen may result in hallucinations and seizures.

Abrupt Withdrawal of Intrathecal Therapy

Abrupt discontinuance of intrathecal baclofen has resulted in high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity; in rare cases, progression to rhabdomyolysis, multisystem organ failure, and death have occurred.

Symptoms usually appear within hours to days following interruption of therapy. Early symptoms may include return of baseline spasticity, pruritus, hypotension, and paresthesias. Advanced withdrawal syndrome may resemble autonomic dysreflexia, sepsis, malignant hyperthermia, neuroleptic malignant syndrome, or other conditions associated with a hypermetabolic state or widespread rhabdomyolysis.

Rapid, accurate diagnosis and treatment in emergency room or intensive care setting are needed to prevent potentially life-threatening CNS and systemic effects.

Restore intrathecal baclofen therapy at or near the dosage used prior to interruption.

If reinstitution of intrathecal delivery is delayed, drugs that enhance GABA effects (e.g., oral or enteral baclofen; oral, enteral, or IV benzodiazepines) may prevent potentially fatal sequelae. However, do not rely on oral or enteral baclofen alone to halt progression of intrathecal baclofen withdrawal.

Experience in Intrathecal Administration

Should be administered intrathecally only by qualified individuals familiar with the administration techniques and patient management problems.

Initial test for responsiveness to intrathecal baclofen, implantation of pump, and subsequent periods of dosage titration must be performed in a medically supervised setting that is adequately equipped for the management of potential complications; resuscitative equipment should be readily available.

Risks of Intrathecal Administration

Potentially life-threatening CNS depression, cardiovascular collapse, and respiratory failure reported following intrathecal administration. Fatalities (including one case of unexpected death after administration of 3 test doses and 2 cases of sudden and unexpected death occurring within 2 weeks of pump implantation) reported rarely during intrathecal therapy; however, manufacturer states that causal relationship not established.

Patients, caregivers, and health-care providers should receive adequate information regarding the risks of intrathecal baclofen therapy, including information on recognition and management of potential overdosage and proper care of the pump and catheter insertion site.

Management of Controlled Infusion Device

Delay implantation of controlled-infusion device until response to test dose(s) is adequately evaluated.

Familiarization with the implantable infusion device (e.g., instructions and precautions for pump programming and refilling) is essential.

Fill drug reservoir under aseptic conditions (to avoid bacterial contamination and serious infection), following the directions provided by the device’s manufacturer; only fully trained and qualified personnel should fill reservoir. Follow proper refill frequency to avoid depletion of drug reservoir during use.

Monitor patient carefully, particularly during the initial phase of pump use, dosage titration, and reservoir refilling to ensure an acceptable, reasonably stable response.

Any sudden increase in dosage requirement should suggest the possibility of pump and/or catheter malfunction (i.e., catheter kink or dislodgement). If no increase in response is observed with upward titration of dosage, check pump function and catheter patency.

Intrathecal Baclofen Overdose

Signs of intrathecal baclofen overdose may appear suddenly or over a period of time.

Acute, massive overdose may present as coma.

Less sudden and/or less severe forms of overdose may present with drowsiness, lightheadedness, dizziness, somnolence, respiratory depression, seizures, rostral progression of hypotonia, and loss of consciousness progressing to coma.

Overdose generally related to pump malfunction or dosing error.

If overdose appears likely, immediately take patient to hospital for assessment and emptying of pump reservoir.

Fill pump with extreme caution; refill only through the pump reservoir refill septum. If reservoir refill septum is not properly accessed, inadvertent injection into sub-Q tissue can occur, possibly resulting in life-threatening overdosage or early depletion of reservoir. Some pumps are equipped with a catheter access port that allows direct access to the intrathecal catheter; direct injection into this catheter may cause life-threatening overdosage.

General Precautions

Autonomic Dysreflexia

Use intrathecal baclofen with caution in patients with a history of autonomic dysreflexia; the presence of nociceptive stimuli or abrupt withdrawal of therapy may precipitate episode of dysreflexia.

CNS Depression

Risk of sedation and/or drowsiness. Performance of activities requiring mental alertness may be impaired.

Concurrent use of other CNS depressants may potentiate CNS depression. (See Specific Drugs under Interactions.)

Maintenance of Muscle Tone

Use with caution and titrate dosage carefully when spasticity is necessary to sustain upright posture and balance in locomotion or whenever spasticity is used to obtain increased or optimal body function.

Neurological Disorders

Possible exacerbation of psychotic disorders, schizophrenia, or confusional states; use with caution and monitor such patients carefully.

Possible deterioration in seizure control and EEG in epileptic patients; monitor patient’s clinical state and EEG at regular intervals.

Concomitant Antispasmodic Therapies

If intrathecal therapy is to be employed, attempt to discontinue concomitant oral antispasmodic drugs to avoid possible overdose and drug interactions, either prior to screening phase or following implantation of infusion device. Monitor patient carefully; avoid abrupt dosage reduction or discontinuance of concomitant antispasmodics.

Presence of Infection

Presence of infection may interfere with assessment of the patient’s response to baclofen test dose(s), increase surgical complications after pump implantation, and complicate attempts to adjust dosage.

Patients being considered for intrathecal baclofen therapy should be without concurrent infection.

Intrathecal Mass

Development of intrathecal mass at the tip of implanted catheter reported following long-term intrathecal baclofen therapy. Most common sequelae or manifestations include decreased therapeutic response (i.e., worsening spasticity, return of spasticity despite previous response, withdrawal symptoms, poor response to escalating doses, frequent or large dosage increases), pain, and neurologic deficit or dysfunction.

Monitor patients carefully for any new neurologic manifestations. If new neurologic manifestations suggestive of an intrathecal mass occur, consider neurosurgical consultation, since many symptoms of inflammatory mass are similar to those associated with severe spasticity. In some cases, an imaging procedure may be appropriate to confirm or rule out diagnosis of an intrathecal mass.

Ovarian Cysts

Ovarian cysts found in about 4% of multiple sclerosis patients receiving oral baclofen for up to 1 year; cysts disappeared spontaneously despite continued baclofen use in most patients. Estimated rate of occurrence in healthy females is approximately 1–5%.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk following oral administration; not known whether baclofen distributes into milk following intrathecal administration.

Nursing not recommended in women receiving oral baclofen. Women receiving intrathecal baclofen should nurse infant only if potential benefit justifies potential risks to infant.

Pediatric Use

Safety and efficacy of oral baclofen not established in children <12 years of age.

Safety and efficacy of intrathecal baclofen not established in children <4 years of age.

Children being considered for intrathecal therapy should have sufficient body mass to accommodate the pump. Consult directions provided by the device’s manufacturer.

Renal Impairment

Excreted principally in urine as unchanged drug; use with caution in patients with impaired renal function. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

For oral baclofen, drowsiness, dizziness, weakness, fatigue.

For intrathecal baclofen in patients with spasticity of spinal cord origin, somnolence, dizziness, nausea, hypotension, headache, seizures, hypotonia.

For intrathecal baclofen in patients with spasticity of cerebral origin, agitation, constipation, somnolence, leukocytosis, chills, urinary retention, hypotonia.

Drug Interactions

Specific Drugs

Insufficient experience with concomitant use of intrathecal baclofen and other drugs to predict specific drug-drug interactions.

Baclofen Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed following oral administration, with peak blood concentrations attained within 2–3 hours. GI absorption is reduced as dosage is increased.

Following intrathecal administration, plasma concentrations are 100 times less than those achieved following oral administration.

Onset

Oral administration: Onset in hours to weeks.

Intrathecal injection: Onset in 0.5–1 hour in adults; peak effect in about 4 hours.

Continuous intrathecal infusion: Onset at 6–8 hours in adults; peak effect at 24–48 hours.

Onset and peak response may vary depending on dose and severity of symptoms.

Duration

Following intrathecal injection, effects may last 4–8 hours. Duration may vary depending on dose and severity of symptoms.

Distribution

Extent

Widely distributed following oral administration, but only small amounts cross the blood-brain barrier.

Crosses the placenta and distributes into milk following oral administration.

Plasma Protein Binding

30%.

Elimination

Metabolism

About 15% of a dose is metabolized in the liver, mostly by deamination.

Elimination Route

Excreted mainly (70–80%) in urine as unchanged drug or metabolites; remainder is excreted in feces.

Half-life

Serum half-life: 2.5–4 hours.

CSF elimination half-life: 1.51 hours for the first 4 hours following intrathecal injection. Following intrathecal administration, CSF clearance of baclofen approximates CSF turnover.

Stability

Storage

Oral

Tablets

Well-closed containers at 20–25°C.

Parenteral

Injection

≤30°C. Refrigeration not required. Do not freeze or autoclave.

Compatibility

Parenteral

Solution Compatibility113

Drug Compatibility

Actions

• Decreases frequency and amplitude of muscle spasms (tonic reflexes) that arise in response to muscle stretching in patients with various spinal cord lesions.

• Simultaneously and equally suppresses cutaneous reflexes and muscle tone but only slightly depresses amplitude of tendon jerks (phasic reflexes).

• Inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possibly by decreasing excitatory neurotransmitter release from primary afferent terminals; actions at supraspinal sites also may occur and contribute to drug’s clinical effect.

• Intrathecal administration in animals increases antinociception and decreases muscle rigidity and spasticity.

Advice to Patients

• Importance of not abruptly discontinuing therapy. For patients receiving intrathecal baclofen, importance of keeping scheduled refill visits and of recognizing early signs and symptoms of withdrawal.

• If baclofen is to be administered intrathecally, risks associated with intrathecal baclofen therapy, recognition and management of overdosage, and proper care of pump and catheter insertion site.

• Risk of drowsiness; exercise caution when driving or operating machinery.

• Potential for additive CNS depression if other CNS depressants (e.g., alcohol) are used concomitantly.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of women informing their clinician if they are or plan to become pregnant or to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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