What are the contraindications to baclofen in patients with a history of stroke, cerebral hemorrhage, severe respiratory disease, such as chronic obstructive pulmonary disease (COPD) or asthma, hepatic impairment, or impaired renal function?

Contraindications to Baclofen

Baclofen is absolutely contraindicated in patients with severely impaired renal function (eGFR <30 mL/min/1.73m²) or those on renal replacement therapy, and should be avoided in patients with stroke, as the drug has not shown benefit and demonstrates poor tolerability in this population. 1, 2

Absolute Contraindications

Severe Renal Impairment

• Baclofen must be avoided in patients with eGFR <30 mL/min/1.73m² or those receiving dialysis, as the drug is 69-85% renally cleared and accumulates rapidly even at low doses 2
• Patients with end-stage renal disease develop toxicity within 2-3 days (range: hours to 16 weeks) after starting baclofen, even at doses as low as 5-10 mg daily 3, 4
• Neurotoxicity manifests as altered consciousness, encephalopathy, ataxia, dystonia, and abdominal pain; severe complications include seizures and respiratory depression 4, 5
• Dose reduction is required for moderate renal impairment (eGFR 30-60 mL/min/1.73m²), though specific dosing guidance remains unclear in the literature 1, 2

Stroke Patients

• The FDA label explicitly states that baclofen has not significantly benefited patients with stroke and these patients show poor tolerability 1
• The American Heart Association guidelines recommend botulinum toxin over baclofen for focal spasticity post-stroke, as it is more effective and better tolerated 6, 7
• For generalized spasticity post-stroke, first-line treatment consists of non-pharmacological approaches (positioning, range of motion exercises, stretching, splinting) before considering baclofen 6, 7

Pregnancy-Related Contraindications

• Baclofen must be gradually discontinued before delivery if used during pregnancy to prevent neonatal withdrawal syndrome (increased muscle tone, tremor, jitteriness, seizures) 1
• The drug increases omphaloceles in animal studies at 13 times the human dose and causes incomplete skeletal ossification 1
• Use only if benefit clearly outweighs fetal risk; if continued, parents must be counseled about neonatal withdrawal symptoms 1

Relative Contraindications and High-Risk Conditions

Cerebral Hemorrhage and Brain Injury

• While not explicitly contraindicated, baclofen toxicity presents more severely in patients with brain damage, manifesting as seizures, psychic symptoms, and hyperthermia 8
• The FDA label does not establish efficacy for cerebral palsy, making risk-benefit ratio unfavorable 1

Severe Respiratory Disease (COPD/Asthma)

• Baclofen can cause respiratory depression as a manifestation of CNS toxicity, particularly in overdose situations 4, 8
• The drug acts as a CNS depressant and should be used with extreme caution in patients with compromised respiratory function 8
• Beta-blockers used for other conditions are contraindicated in reactive airway disease and COPD; similar caution applies to CNS depressants like baclofen 9

Hepatic Impairment

• Baclofen may be contraindicated in patients with significant hepatic dysfunction due to potential for increased CNS effects 9
• The drug undergoes minimal hepatic metabolism (15-31% of clearance is non-renal), but hepatic dysfunction may impair the limited metabolism that occurs 3

Critical Safety Warnings

Abrupt Withdrawal Syndrome

• Sudden discontinuation causes hallucinations, seizures, hyperthermia, and potentially death—this is the most dangerous complication of baclofen therapy 1, 8
• For intrathecal baclofen, withdrawal syndrome evolves over 1-3 days and becomes fulminant if not recognized; resuming intrathecal infusion immediately is the only effective treatment 6
• Even high-dose oral baclofen cannot prevent acute withdrawal in patients previously on intrathecal therapy 6
• Always taper baclofen slowly when discontinuing, except in cases of serious adverse reactions requiring immediate cessation 1

Clinical Decision Algorithm

For patients requiring spasticity treatment:

1. First, assess renal function: If eGFR <30 mL/min/1.73m² or on dialysis → Do not use baclofen 2

2. Second, identify the underlying condition:

   • Stroke → Use botulinum toxin for focal spasticity; avoid baclofen 1, 6
   • Multiple sclerosis or spinal cord injury → Baclofen is appropriate 1
   • Cerebral palsy or Parkinson's disease → Efficacy not established; avoid baclofen 1

3. Third, evaluate respiratory status: Severe COPD/asthma → Consider alternative agents due to respiratory depression risk 4, 8

4. Fourth, check pregnancy status: If pregnant → Plan gradual discontinuation before delivery; counsel about neonatal withdrawal 1

5. If baclofen is appropriate: Start at 5-10 mg/day and titrate slowly to 30-80 mg/day divided into 3-4 doses, with regular monitoring for CNS effects 6, 7

Common Pitfalls to Avoid

• Never prescribe baclofen to dialysis patients, even at low doses—toxicity occurs rapidly and requires urgent hemodialysis for reversal 4, 5, 2
• Do not assume standard dosing is safe in elderly patients with unrecognized renal impairment—always check eGFR before prescribing 3
• Recognize that abdominal pain is a common presenting feature of baclofen toxicity in renal failure, not just altered consciousness 4
• Remember that hemodialysis effectively removes baclofen, but consciousness improvement lags several hours after dialysis due to delayed CNS clearance 4