Baclofen

Baclofen is a GABA-B receptor agonist used for spasticity from multiple sclerosis and spinal cord disease, and by intrathecal pump for severe spasticity. It is cleared by the kidney and accumulates dangerously in kidney failure, and abrupt withdrawal, especially of intrathecal baclofen, can be fatal.

Mechanism. Activates presynaptic GABA-B receptors in the spinal cord, reducing release of excitatory neurotransmitters and spinal reflex activity.

Pharmacokinetics. Oral absorption is 70 to 85%. Half-life is 3 to 4 hours. About 70 to 80% is excreted unchanged in urine. Entry into the brain is limited, so intrathecal dosing is much smaller.

First-line use. Spasticity from multiple sclerosis, spinal cord injury and other upper motor neurone lesions. Treatment is long term.

• Adults, oral baclofen: 5 mg three times daily for 3 days, then 10 mg three times daily for 3 days, then 15 mg three times daily for 3 days, then 20 mg three times daily. Usual maintenance 30 to 75 mg daily in three divided doses. Maximum 80 mg daily in most labels (100 mg daily in some).

• Children: 0.3 mg/kg daily in two to four doses, increased weekly to a usual 0.75 to 2 mg/kg daily. Maximum 40 mg daily under 8 years and 60 mg daily at 8 years and over.

• Stop if there is no benefit after a reasonable period at the maximum tolerated dose.

Specialist use. Intrathecal baclofen for severe spasticity: a screening bolus of 50 micrograms, then pump titration over weeks, with usual maintenance of 300 to 800 micrograms daily.

Emergency use. Acute baclofen withdrawal (pump failure or abrupt oral stop) needs immediate restoration of baclofen, with benzodiazepines and intensive care for rising temperature, rebound spasticity, confusion, seizures and rhabdomyolysis.

Kidney, liver, weight and age.

• Kidney: creatinine clearance 50 to 80 mL/min, reduce the dose by one third; 30 to 50 mL/min, by one half; under 30 mL/min, by two thirds, starting at 5 mg once daily. Baclofen is removed by haemodialysis.

• Liver: no adjustment.

• Older adults: start 5 mg once or twice daily.

Contraindications. Hypersensitivity. Use is avoided in active peptic ulcer disease in some labels.

Serious adverse effects. Encephalopathy, coma and respiratory depression in kidney failure or overdose, seizures, withdrawal syndrome (hyperthermia, rebound spasticity, hallucinations, seizures), hypotension and urinary retention.

Common adverse effects. Drowsiness, weakness, dizziness, confusion, nausea, and reduced muscle tone that can worsen function or posture.

Interactions. Alcohol, opioids, benzodiazepines and other sedatives add central depression. Antihypertensives add hypotension. Tricyclic antidepressants may cause marked hypotonia. Levodopa may cause confusion and hallucinations. Lithium levels may rise.

Common prescribing errors. Not reducing the dose in kidney impairment. Stopping abruptly. Prescribing to people who rely on spasticity to stand or walk.

Special groups.

• Pregnancy: avoid unless essential; neonatal withdrawal is reported.

• Breastfeeding: very low milk levels; usually acceptable.

• Older adults: sedation, falls and confusion are frequent.

Formulations. Tablets 5, 10 and 25 mg (market dependent). Oral solution 5 mg/5 mL. Intrathecal ampoules for specialist pumps. Take with food or milk to limit nausea.

Monitoring.

• Baseline creatinine clearance, then yearly and with illness.

• Spasticity, function, sedation, falls and mood. Intrathecal pumps need scheduled refill and alarm checks.

Stopping. Taper over at least 1 to 2 weeks. Never stop intrathecal baclofen abruptly.

Referral and escalation. Refer for poor control on maximum tolerated oral doses (intrathecal pump), toxicity, or suspected withdrawal.