What is the appropriate baclofen dosing for a patient with an estimated glomerular filtration rate of 36 mL/min (stage 3b chronic kidney disease)?

Baclofen Dosing in CKD Stage 3b (GFR 36 mL/min/1.73 m²)

Baclofen should be dose-reduced by approximately 50% in patients with GFR 36 mL/min/1.73 m² (moderate CKD), starting at a maximum of 5 mg twice daily, with careful monitoring for neurotoxicity. 1

Evidence-Based Dose Reduction

The pharmacokinetic study by Soni et al. demonstrates that baclofen clearance decreases proportionally with declining kidney function, requiring a mean dose reduction of approximately 50% in patients with moderate CKD (GFR 30-50 mL/min/1.73 m²) to achieve drug exposure comparable to patients with normal renal function. 1

• Baclofen is primarily renally excreted (69-85% unchanged in urine), making dose adjustment essential in any degree of renal impairment 2, 3
• The area under the curve (AUC) and half-life increase significantly as GFR declines, while oral clearance decreases proportionally 1
• Linear regression analysis shows baclofen clearance correlates directly with creatinine clearance, allowing precise dose calculation based on kidney function 1

Specific Dosing Recommendations

Start with 5 mg twice daily (total 10 mg/day) rather than the standard 15 mg/day initial dose used in patients with normal kidney function. 1

• The standard starting dose in normal renal function is 5 mg three times daily (15 mg/day total) 1
• At GFR 36 mL/min/1.73 m², this represents moderate CKD (Stage 3b), falling into the 30-50 mL/min category requiring approximately 50% dose reduction 1
• Maximum daily dose should not exceed 20-30 mg/day in divided doses, compared to 80 mg/day in normal renal function 4

Clinical Toxicity Risk

Even low doses of baclofen (≥20 mg/day) carry a 3.54-fold increased risk of encephalopathy within 30 days in patients with CKD compared to doses <20 mg/day, with risk increasing progressively at lower GFR values. 4

• At GFR 30-44 mL/min/1.73 m² (which includes your patient's GFR of 36), the absolute risk increase for encephalopathy is 1.23% within 30 days when using ≥20 mg/day 4
• Altered consciousness is the predominant presenting feature of baclofen toxicity, occurring even with short-term therapy at low doses 5
• Abdominal pain occurs in approximately 55% of toxicity cases in renal patients, representing a gamma-aminobutyric acid-mediated cholinergic effect 5
• Severe complications including seizures and respiratory depression are less common but can occur 5

Monitoring Requirements

Monitor closely for early signs of neurotoxicity including confusion, drowsiness, dizziness, ataxia, or abdominal pain within the first week of therapy. 2, 5, 3

• Most patients with impaired renal function develop toxic symptoms within 48 hours to 1 week of initiating therapy, even at low doses 5, 3
• The lag between drug accumulation and symptom onset is short in moderate-to-severe CKD 5
• If toxicity develops, hemodialysis is effective in clearing baclofen and shortening recovery time to approximately 2.7 days versus 9 days with supportive care alone 5

Critical Contraindications

The American Journal of Kidney Diseases recommends avoiding baclofen entirely in patients with severely reduced kidney function (GFR <30 mL/min/1.73 m²) or those on renal replacement therapy. 2

• While your patient's GFR of 36 mL/min/1.73 m² falls just above this threshold, extreme caution is warranted 2
• Any further decline in kidney function would move the patient into the "avoid use" category 2
• Consider alternative muscle relaxants with less renal dependence if clinically appropriate 2

Practical Dosing Algorithm

1. Initial dose: 5 mg twice daily (morning and evening) 1
2. Titration: If needed after 3-7 days and no toxicity observed, may increase by 5 mg/day increments every 3-7 days 1
3. Maximum dose: Do not exceed 20 mg/day total in divided doses 4, 1
4. Monitoring: Assess for confusion, drowsiness, dizziness, or abdominal pain at each dose increase 5, 3
5. Discontinuation: Stop immediately if any neurotoxic symptoms develop and consider hemodialysis if severe 2, 5