Baclax

Approved Indications:

• Spasticity (moderate to severe) associated with:
• Multiple sclerosis
• Spinal cord injury or disease (e.g., traumatic lesions, transverse myelitis)
• Cerebral palsy‐associated spasticity in pediatric and adult patients
• Spinal cord disorders (e.g., motor neuron disease, spinal syringomyelia)
• Post‐stroke spasticity (under specialist supervision)
• Relief of flexor spasms, muscle rigidity, and clonus in neurological conditions

Clinically Accepted Off‑Label Uses:

• Alcohol use disorder (AUD): Used off-label to reduce craving and manage associated spasticity
• Persistent hiccups (especially >48 hours) with suspected central nervous origin
• Trigeminal neuralgia: Adjunct in refractory cases
• Restless legs syndrome (RLS)
• Spasticity management in pediatric cerebral palsy, under expert supervision

Route: Oral or Intrathecal (pump implant)

Oral Baclofen

• Adults:
• Initiate at 5 mg three times daily
• Increase every 3 days by 5 mg per dose
• Typical maintenance: 40–80 mg/day in divided doses
• Maximum: 80 mg/day
• Children (≥2 years):
• Start 0.3 mg/kg/day in divided doses
• Titrate based on efficacy/tolerance
• Maximum: 1.5–2 mg/kg/day or 40 mg/day (whichever is lower)
• Elderly:
• Begin at 5 mg once or twice daily
• Taper slowly to minimize CNS side effects

Intrathecal Baclofen

• Test dose: 25–50 mcg via lumbar puncture
• Maintenance range: 50–800 mcg/day (individualized, continuous infusion)

Renal Impairment:

• Use caution; reduce dose and monitor for sedation or weakness

Hepatic Impairment:

• No formal adjustment, but monitor liver function if prolonged therapy

Duration:

• Long‑term therapy may be needed; taper gradually to discontinue safely

Baclofen is a GABAB receptor agonist that acts at the spinal cord level. By binding to pre‑ and postsynaptic GABAB receptors in the dorsal horn, it inhibits calcium influx and reduces release of excitatory neurotransmitters like glutamate. Postsynaptic hyperpolarization decreases neuronal excitability. The result is reduced muscle spasticity, diminished reflex activity, and skeletal muscle relaxation—without direct action on the muscle fibers themselves.

• Absorption: Rapid and nearly complete oral absorption; peak concentration in ~2–3 hours
• Bioavailability: Approximately 70–80%
• Distribution: Volume of distribution ~0.7 L/kg; crosses blood–brain barrier slowly
• Protein Binding: Low (~30%)
• Metabolism: Approximately 15% hepatic deamination
• Half‑Life: 2.5–4 hours
• Elimination: Primarily excreted unchanged in urine (60–80%)
• Onset: Oral effect within hours; onset faster via intrathecal route (30–60 minutes)
• Steady State: Achieved within 2–3 days of stable oral dosing

Pregnancy:

• FDA Category C
• Animal studies suggest possible fetal harm; human data limited
• Use only if benefits outweigh potential risks

Lactation:

• Passes into breast milk in low concentrations
• Monitor infants for sedation or feeding difficulties
• Use caution or avoid high-dose therapy while breastfeeding

• Primary Class: Skeletal Muscle Relaxant
• Subclass: Central GABAB receptor agonist
• Generation: First‑generation specific to GABAB mechanism

• Known hypersensitivity to baclofen or formulation excipients
• History of psychosis or acute confusional states
• Severe renal impairment (e.g., creatinine clearance <30 mL/min) without dose adjustment
• Abrupt discontinuation of intrathecal baclofen pump (withdrawal risk)

• Withdrawal syndrome (especially intrathecal): May include seizures, rebound spasticity, high fever, altered mental status, rhabdomyolysis—taper gradually
• CNS depression: Use cautiously in elderly, respiratory compromise, or with other sedatives
• Seizure risk: May lower seizure threshold
• Psychiatric disturbances: Potential for hallucinations or confusion
• Renal impairment: Risk of accumulation; monitor dosing
• Driving/machinery: May impair motor skills and alertness

Common (CNS/Systemic):

• Drowsiness, dizziness, fatigue, weakness, confusion
• Muscle hypotonia

Gastrointestinal:

• Nausea, constipation

Less Common:

• Insomnia, ataxia, tremor, urinary retention/incontinence

Serious or Rare:

• Respiratory depression (especially intrathecal use)
• Seizures (particularly upon withdrawal)
• Psychosis, hallucinations
• Anaphylaxis (rare)
• Hepatotoxicity (very rare)

Timing & Severity:

• Usually appear within the first week or after dose escalation
• CNS side effects are dose-related and reversible

• CNS depressants (e.g., benzodiazepines, opioids, alcohol): Additive sedation and respiratory depression
• Antihypertensives: May potentiate hypotensive effects
• Tricyclic antidepressants or MAO inhibitors: Potential for enhanced CNS depression
• Levodopa: May reduce dopaminergic effectiveness; heightened confusion
• Neuromuscular blockers: Potential additive effect in presence of high systemic baclofen (rare)

Enzyme Interaction:

• Baclofen is not significantly metabolized via CYP450, so enzyme-mediated interactions are minimal

• New consensus guidelines reinforce slow tapering, particularly of intrathecal baclofen, to prevent severe withdrawal syndrome
• European and U.S. neurological associations expand off-label use recommendations for persistent hiccups and alcohol‑use disorder
• Intrathecal baclofen pumps now more widely endorsed in severe refractory spasticity, especially cerebral palsy and multiple sclerosis
• Ongoing development of long‑acting oral and intrathecal formulations

Oral Tablets/Suspension:

• Temperature: 20°C–25°C (68°F–77°F); allowed excursion within 15°C–30°C
• Store in airtight, dry container
• Protect from moisture and light
• Keep out of children’s reach

Intrathecal Solution (Pump Vial):

• Refrigerate at 2°C–8°C (36°F–46°F) until used
• Protect from light
• Do not freeze
• Use aseptic technique when filling the pump reservoir
• Discard open vials per local policy