Is baclofen (GABA receptor agonist) safe to use in patients with rhabdomyolysis?

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Baclofen Safety in Rhabdomyolysis

Baclofen should be avoided in patients with rhabdomyolysis due to the risk of accumulation and toxicity in the setting of acute kidney injury, which is the most serious complication of rhabdomyolysis.

Primary Concern: Renal Dysfunction and Drug Accumulation

  • Rhabdomyolysis frequently causes acute renal failure (ARF), occurring in approximately 10% of all ARF cases, making renally-excreted drugs particularly dangerous 1, 2.

  • Baclofen is primarily eliminated via the kidneys, and toxicity becomes a serious risk when kidney function is impaired 3.

  • In patients with severely reduced kidney function (eGFR <30 mL/min/1.73m²) or those requiring renal replacement therapy, baclofen should be avoided entirely 3.

  • Even with moderately reduced kidney function (eGFR 30-60 mL/min/1.73m²), baclofen dosing must be significantly reduced 3.

Clinical Manifestations of Baclofen Toxicity

  • Baclofen toxicity presents with neurotoxicity (drowsiness, dizziness, sedation, altered mental status) and hemodynamic instability, which can be life-threatening 3, 4.

  • Central nervous system depression from baclofen can worsen the clinical picture in rhabdomyolysis patients who may already have altered mental status from electrolyte abnormalities, myoglobinemia, or uremia 5, 2.

  • Baclofen may also worsen obstructive sleep apnea by promoting upper airway collapse, adding respiratory risk 4, 6.

Withdrawal Risk Considerations

  • Abrupt discontinuation of baclofen can cause potentially life-threatening withdrawal symptoms including hallucinations, delirium, seizures, fever, tremors, tachycardia, and autonomic instability 4, 6.

  • This creates a clinical dilemma: continuing baclofen risks toxicity in the setting of renal dysfunction, but stopping it abruptly risks severe withdrawal 4.

Management Algorithm for Patients on Baclofen Who Develop Rhabdomyolysis

  1. Immediately assess kidney function (creatinine, eGFR, urine output) and creatine kinase levels to determine severity 1, 7.

  2. If eGFR <30 mL/min/1.73m² or patient requires dialysis: Hold baclofen and consider urgent hemodialysis if toxicity symptoms are present, as hemodialysis effectively removes baclofen 3.

  3. If eGFR 30-60 mL/min/1.73m²: Reduce baclofen dose by at least 50-75% and monitor closely for toxicity symptoms 3.

  4. If patient has been on chronic baclofen: Taper slowly rather than stopping abruptly, even in the setting of renal dysfunction, to avoid withdrawal complications 4, 6.

  5. Initiate aggressive intravenous fluid resuscitation (the only conditionally recommended treatment for rhabdomyolysis) to prevent further renal deterioration 1.

Alternative Muscle Relaxant Considerations

  • If muscle spasm management is essential during rhabdomyolysis recovery, consider alternatives with less renal dependence 8.

  • Benzodiazepines may be used for muscle spasm relief, though they carry their own risks of sedation and respiratory depression, particularly when combined with other CNS depressants 8.

  • Non-pharmacological interventions (positioning, range of motion exercises, stretching) should be prioritized when possible 6.

Key Clinical Pitfalls to Avoid

  • Do not continue standard baclofen dosing in patients with rhabdomyolysis-induced renal dysfunction—this will lead to drug accumulation and toxicity 3.

  • Do not abruptly stop baclofen in chronic users without a tapering plan, even if renal function is compromised 4, 6.

  • Do not assume normal kidney function persists—monitor creatinine and CK levels serially, as renal dysfunction can develop or worsen rapidly in rhabdomyolysis 1, 7, 2.

  • Do not combine baclofen with other CNS depressants (opiates, benzodiazepines) in this setting, as this increases risk of respiratory depression and altered mental status 4, 5.

References

Research

Clinical features, pathogenesis and management of drug-induced rhabdomyolysis.

Medical toxicology and adverse drug experience, 1989

Research

Baclofen Toxicity in Kidney Disease.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2018

Guideline

Baclofen's Mechanism and Clinical Application in Esophageal Motility Disorders

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Drug induced rhabdomyolysis: case report.

East African medical journal, 1997

Guideline

Baclofen Use in Dementia Patients with Muscle Contraction

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Rhabdomyolysis: A syndrome to be considered.

Medicina clinica, 2022

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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