Baclofen
Baclofen
Generic Name
Baclofen
Mechanism
- Selective activation of GABA_B receptors in the spinal cord’s interneurons → ↓ excitatory neurotransmitter release.
- Reduces the discharge of motor neurons, thereby diminishing stretch‑reflex activity.
- The inhibition of calcium influx at presynaptic terminals leads to decreased transmitter release and attenuation of hyperexcitability.
Pharmacokinetics
| Parameter | Description |
| Absorption | Rapid oral absorption, 75‑85 % bioavailability. Peak plasma concentration at 1–2 h. |
| Distribution | 20‑50 % bound to plasma proteins; readily crosses blood–brain barrier. |
| Metabolism | Minimal hepatic metabolism (mainly glucuronidation). |
| Elimination | Primarily renal (kidney clearance). Half‑life ~ 4–6 h; extended to 12–18 h in renal impairment. |
| Drug Interactions | Potentiated by CNS depressants (opioids, benzodiazepines); can inhibit CYP3A4/2D6 when used with high‑dose baclofen patches (rare). |
Indications
- Spasticity
- Multiple sclerosis
- Spinal cord injury
- Cerebral palsy
- Off‑label (strong evidence)
- Alcohol use disorder (as hospital adjunct)
- Chronic neuropathic pain
- Severe vertigo or vestibular migraine (limited data)
Contraindications
- Contraindications
- Hypersensitivity to baclofen or any excipient
- Severe renal dysfunction (eGFR < 30 mL/min/1.73 m²) – risk of drug accumulation
- Warnings
- CNS depression: especially with concomitant sedatives, opioids, or alcohol.
- Renal impairment: dose adjustment required; monitor for toxicity.
- Pregnancy & lactation: category C; caution advised.
Dosing
| Indication | Starting Dose | Titration | Maximum Dose | Route |
| Spasticity | 5 mg PO TID (15 mg/day) | Increase 5 mg TID every 3–5 days | 80 mg/day (≈ 60 mg/day TID) | Oral capsule/tablet |
| Alcohol use disorder | 30 mg PO BID | Adjust per tolerance | 120 mg/day | Oral |
| Patching (pain/spasticity) | 8 mg/24 h patch (8‑mL per 1 day) | 16 mg/24 h as needed | 20 mg/24 h | Transdermal |
• Administration notes: Take with food to reduce GI distress.
• Titration: Increase cautiously; watch for dizziness, drowsiness, and hallucinations.
• Discontinuation: Stop abruptly if severe CNS depression occurs; do not taper rapidly unless required.
Monitoring
- Renal function: Serum creatinine/eGFR every 2–4 weeks for dose‑adjusted patients.
- Neurologic status: Spasticity scales (Modified Ashworth) initially and quarterly.
- Sedation: Evaluate mental status and respiratory rate; adjust dose or discontinue if > 4 h drowsiness.
- Blood counts: CBC if long‑term use > 3 months to detect rare thrombocytopenia.
- Adherence: Review pill counts or patch usage logs.
Clinical Pearls
- Start low, go slow: A 5 mg TID baseline allows gradual titration avoiding exaggerated CNS depression.
- Patch synergy: For patients with poor oral tolerance, a 8 mg/24 h transdermal patch can provide steady plasma levels with minimal GI upset; reserve higher doses for refractory pain.
- Renal grace‑period: In CKD, maintain a maintenance dose of 4 mg TID and monitor eGFR; stop patch use entirely if eGFR < 15 mL/min/1.73 m².
- Alcohol combination: Baclofen’s anti‑alcohol effect is most potent when added to an opioid‑based naltrexone regimen; schedule a dose check at 4 weeks.
- Overdose signs: Look for "red flags" – miosis, hypoventilation, and dry, flushed skin; manage with supportive care and, if available, acute hemodialysis.
- Adverse event check‑list: Use a simple spreadsheet for adverse effect frequency to quickly decide on dose adjustment.
Key take‑away: Baclofen is a potent, versatile GABA_B agonist that, when titrated carefully, offers relief for spasticity and select chronic neuropathic conditions—always mind the renal link and concomitant CNS depressants.
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