LIORESAL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LIORESAL (LIORESAL).

How it works

GABA-B receptor agonist; inhibits monosynaptic and polysynaptic reflexes at the spinal cord level by reducing excitatory neurotransmitter release.

What the body does with it

Metabolism	Hepatic metabolism via deamination (minor pathway); primarily excreted unchanged in urine (70-80% as parent drug, 15% as metabolites).
Excretion	Renal: approximately 70-80% of the dose as unchanged drug and metabolites (primarily glucuronide conjugate); minor biliary/fecal elimination (<5%).
Half-life	Terminal elimination half-life: 2.5-4 hours. Clinically, accumulation occurs in renal impairment, requiring dose adjustment.
Protein binding	~30%; primarily bound to albumin.
Volume of Distribution	0.5-1.0 L/kg; indicates moderate tissue distribution, with higher CNS penetration when administered intrathecally.
Bioavailability	Oral: 70-80% (first-pass effect minimal); intrathecal: nearly 100% due to direct CSF administration.
Onset of Action	Oral: 30-60 minutes to peak effect; intrathecal: 0.5-1 hour for spasticity reduction.
Duration of Action	Oral: 4-8 hours; intrathecal: 8-12 hours with continuous infusion or bolus. Note: duration may be shorter in patients with high spasticity tolerance.

Classification & Brands

Action Class

Skeletal muscle relaxant- Centrally acting

Dosing & administration

Oral: Initial 5 mg 3 times daily, increase by 5 mg per dose every 3 days to a maximum of 80 mg/day (20 mg 4 times daily). Intrathecal: Test dose 50-100 mcg; maintenance infusion 300-800 mcg/day.

Dosage form	INJECTABLE
Renal impairment	GFR >60 mL/min: no adjustment; GFR 30-60: reduce dose by 25-50%; GFR <30: avoid or reduce by 75%; hemodialysis: supplement dose after dialysis.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use.
Pediatric use	Oral: 2.5 mg 4 times daily initially, increase by 2.5-5 mg every 3 days to max 40 mg/day (2-7 years) or 60 mg/day (8-15 years). Intrathecal: test dose 25-50 mcg; maintenance 100-1000 mcg/day.
Geriatric use	Start at 5 mg twice daily; increase slowly due to increased CNS sensitivity; monitor for sedation and confusion.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LIORESAL (LIORESAL).

Breastfeeding	Lioresal (baclofen) is excreted into human breast milk in low concentrations; M/P ratio is approximately 0.4-0.7. No adverse effects reported in nursing infants. Caution advised, especially in preterm infants or those with renal impairment.
Teratogenic Risk	First trimester: Increased risk of orofacial clefts (cleft palate) based on animal studies and limited human data. Second and third trimesters: Risk of fetal bradycardia, hypotonia, and withdrawal symptoms (irritability, tremors) in neonates. Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Abrupt discontinuation of intrathecal baclofen may result in life-threatening withdrawal reactions (high fever, altered mental status, severe spasticity, rhabdomyolysis, autonomic dysfunction).

Side Effect Profile

Serious Effects

Absolute Contraindications

Absolute: Hypersensitivity to baclofen or any component; concomitant use of oral baclofen and intrathecal baclofen; intrathecal use contraindicated in patients with IV access device infection, spinal canal obstruction, or bleeding diathesis. Relative: Renal impairment, hepatic impairment, respiratory insufficiency, seizure disorder, history of autonomic dysreflexia, pregnancy, and lactation.

Clinical Precautions

Precautions

Abrupt discontinuation: may cause withdrawal symptoms (hallucinations, seizures, hyperthermia, rebound spasticity). Sedation: may impair ability to drive or operate machinery. Renal impairment: dose adjustment required. Avoid concomitant use with CNS depressants (alcohol, benzodiazepines). Caution in stroke patients, respiratory depression, psychiatric disorders, epilepsy, and pregnancy.

Clinical Tips & Counseling

Drug interactions

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LIORESAL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LIORESAL (LIORESAL).

How it works

GABA-B receptor agonist; inhibits monosynaptic and polysynaptic reflexes at the spinal cord level by reducing excitatory neurotransmitter release.

What the body does with it

Metabolism	Hepatic metabolism via deamination (minor pathway); primarily excreted unchanged in urine (70-80% as parent drug, 15% as metabolites).
Excretion	Renal: approximately 70-80% of the dose as unchanged drug and metabolites (primarily glucuronide conjugate); minor biliary/fecal elimination (<5%).
Half-life	Terminal elimination half-life: 2.5-4 hours. Clinically, accumulation occurs in renal impairment, requiring dose adjustment.
Protein binding	~30%; primarily bound to albumin.
Volume of Distribution	0.5-1.0 L/kg; indicates moderate tissue distribution, with higher CNS penetration when administered intrathecally.
Bioavailability	Oral: 70-80% (first-pass effect minimal); intrathecal: nearly 100% due to direct CSF administration.
Onset of Action	Oral: 30-60 minutes to peak effect; intrathecal: 0.5-1 hour for spasticity reduction.
Duration of Action	Oral: 4-8 hours; intrathecal: 8-12 hours with continuous infusion or bolus. Note: duration may be shorter in patients with high spasticity tolerance.

Classification & Brands

Action Class

Skeletal muscle relaxant- Centrally acting

Dosing & administration

Oral: Initial 5 mg 3 times daily, increase by 5 mg per dose every 3 days to a maximum of 80 mg/day (20 mg 4 times daily). Intrathecal: Test dose 50-100 mcg; maintenance infusion 300-800 mcg/day.

Dosage form	INJECTABLE
Renal impairment	GFR >60 mL/min: no adjustment; GFR 30-60: reduce dose by 25-50%; GFR <30: avoid or reduce by 75%; hemodialysis: supplement dose after dialysis.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use.
Pediatric use	Oral: 2.5 mg 4 times daily initially, increase by 2.5-5 mg every 3 days to max 40 mg/day (2-7 years) or 60 mg/day (8-15 years). Intrathecal: test dose 25-50 mcg; maintenance 100-1000 mcg/day.
Geriatric use	Start at 5 mg twice daily; increase slowly due to increased CNS sensitivity; monitor for sedation and confusion.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LIORESAL (LIORESAL).

Breastfeeding	Lioresal (baclofen) is excreted into human breast milk in low concentrations; M/P ratio is approximately 0.4-0.7. No adverse effects reported in nursing infants. Caution advised, especially in preterm infants or those with renal impairment.
Teratogenic Risk	First trimester: Increased risk of orofacial clefts (cleft palate) based on animal studies and limited human data. Second and third trimesters: Risk of fetal bradycardia, hypotonia, and withdrawal symptoms (irritability, tremors) in neonates. Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Abrupt discontinuation of intrathecal baclofen may result in life-threatening withdrawal reactions (high fever, altered mental status, severe spasticity, rhabdomyolysis, autonomic dysfunction).