Is baclofen a safer option for an older adult with impaired renal function (creatinine clearance <30 mL/min)?

Baclofen is NOT a Safer Option for Older Adults with Severe Renal Impairment

Baclofen should be avoided entirely in patients with creatinine clearance <30 mL/min due to high risk of neurotoxicity, even at low doses. The FDA label explicitly warns that baclofen is primarily excreted unchanged through the kidneys and requires caution with dose reduction in renal impairment 1. However, the clinical evidence demonstrates that even dose reduction is insufficient to prevent toxicity in severe renal dysfunction.

Evidence Against Baclofen Use in Severe Renal Impairment

Primary Renal Excretion Creates Dangerous Accumulation

• Baclofen is eliminated almost entirely by the kidneys, making accumulation inevitable when creatinine clearance falls below 30 mL/min 1, 2.
• The FDA specifically warns that "because baclofen is primarily excreted unchanged through the kidneys, it should be given with caution, and it may be necessary to reduce the dosage" in impaired renal function 1.
• However, this conservative FDA language understates the actual clinical risk demonstrated in practice.

Clinical Evidence Shows High Toxicity Risk

• A comprehensive literature review of 41 patients with renal insufficiency found that baclofen toxicity occurred at mean doses as low as 20 mg daily (range 5-60 mg), with symptoms starting 2-3 days after initiation 3.
• The majority of affected patients (62.9%) were on dialysis, and 62.5% were elderly (>60 years) 3.
• Expert consensus from nephrology literature explicitly recommends avoiding baclofen use entirely in patients with severely reduced kidney function (eGFR <30 mL/min) or on renal replacement therapy 2.

Even Single Doses Can Cause Severe Toxicity

• A case report documented severe neurotoxicity from a single 25 mg baclofen tablet in a patient with end-stage renal disease, resulting in altered mental status and unconsciousness 4.
• Another case series found that patients with severely impaired renal function developed toxic symptoms "soon after initiating a low-dose baclofen regimen," with the accumulated dosage being small 5.

Clinical Manifestations of Baclofen Toxicity

Neurotoxicity is the Predominant Feature

• Altered consciousness and encephalopathy are the major presenting features in patients with renal impairment 3, 6, 5.
• Additional neurologic symptoms include confusion, generalized hypotonia, tremor, jitteriness, and seizures 1, 6.
• Abdominal pain was noted in 31% of cases (5 of 9 patients in one series), likely due to GABA-mediated cholinergic effects 5.

Hemodynamic Instability Can Occur

• Patients may develop hemodynamic instability requiring intensive care monitoring 2, 6.
• Severe complications, while less common, include seizures and respiratory depression 5.

Management of Baclofen Toxicity

Hemodialysis is the Primary Treatment

• Hemodialysis is the most effective treatment modality for baclofen elimination, used in 65.7% of reported cases 3.
• Early hemodialysis (<48 hours) significantly shortens recovery time compared to supportive care alone (2.71 ± 0.42 days vs. 9 days, p < 0.01) 5.
• Multiple hemodialysis sessions may be required for complete resolution, with recovery times ranging from 2 hours with dialysis to 8 days with conservative treatment 3, 6.

Important Clinical Pitfall

• A lag of several hours between the end of hemodialysis and improvement in consciousness is common, likely due to delayed clearance from the central nervous system 5.
• This delay should not be misinterpreted as treatment failure.

Practical Recommendations

Absolute Contraindication in Severe Renal Impairment

• Do not prescribe baclofen to patients with CrCl <30 mL/min or those on dialysis 2.
• The literature concludes that "the administration of baclofen, regardless of the dosage, in these patients is not appropriate" 5.

Dose Reduction in Moderate Impairment

• For patients with moderately reduced kidney function (eGFR 30-60 mL/min/1.73m²), significant dose reduction is required 2.
• Even with dose adjustment, close monitoring for early signs of neurotoxicity is essential.

Alternative Therapies Should Be Sought

• Given the high risk-to-benefit ratio, clinicians should actively seek alternative treatments for muscle spasm and spasticity in patients with renal impairment 4.
• The risk of severe neurotoxicity, hemodynamic instability, and potential need for emergent dialysis outweighs any therapeutic benefit in this population.