Can I give tizanidine (Zanaflex) to a patient on hemodialysis (HD) with End-Stage Renal Disease (ESRD) and impaired renal function (GFR of 13) for back spasms?

Tizanidine Use in Hemodialysis Patients with ESRD

Tizanidine should be avoided in patients on hemodialysis with ESRD and GFR of 13 due to significantly reduced clearance and risk of adverse effects. 1

Pharmacokinetics and Renal Considerations

• Tizanidine clearance is reduced by more than 50% in patients with renal insufficiency (creatinine clearance < 25 mL/min), leading to drug accumulation and prolonged clinical effects 1
• The FDA label specifically cautions against use in patients with renal insufficiency, stating that tizanidine "should be used with caution in patients with renal insufficiency" 1
• In patients with ESRD on hemodialysis, tizanidine can accumulate to toxic levels, as demonstrated by case reports of severe bradycardia in hemodialysis patients even at low doses (3 mg/day) 2

Potential Adverse Effects in ESRD Patients

• Symptomatic bradycardia has been reported in hemodialysis patients taking tizanidine, with higher than expected trough concentrations 2
• Tizanidine can cause significant hypotension, which may be particularly problematic in hemodynamically unstable dialysis patients 1
• Sedation and drowsiness are common side effects that may be exacerbated in patients with renal impairment due to drug accumulation 1, 3

Alternative Options for Back Spasms in ESRD

• Baclofen can be used for back spasms in patients with renal impairment, but the dosage should be adjusted by increasing the dosing interval rather than decreasing the dose 4
• The Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement recommends continuing baclofen in patients with renal impairment, including on the day of procedures 4
• For patients with muscle spasms and ESRD, medication selection should prioritize drugs that are not primarily renally cleared 4, 5

Management Algorithm for Muscle Relaxants in ESRD

1. First, assess if medication is necessary:

   • Consider non-pharmacological approaches (physical therapy, heat therapy) 6

2. If medication is needed:

   • Choose muscle relaxants that are not primarily renally cleared 4
   • Avoid tizanidine due to >50% reduction in clearance in renal insufficiency 1
   • Consider baclofen with appropriate dosage adjustment 4

3. If tizanidine must be used (which is not recommended):

   • Start with the lowest possible dose (1 mg once daily) 1
   • Monitor closely for adverse effects including hypotension, bradycardia, and excessive sedation 1, 2
   • Increase individual doses rather than dosing frequency if higher doses are required 1
   • Ensure administration after hemodialysis sessions 5, 7

Common Pitfalls to Avoid

• Failing to recognize drug accumulation: Patients with ESRD often have unpredictable drug levels due to altered pharmacokinetics 7
• Overlooking cardiovascular effects: Tizanidine can cause significant hypotension and bradycardia, which may be particularly dangerous in hemodynamically unstable dialysis patients 1, 2
• Inadequate monitoring: ESRD patients taking centrally-acting muscle relaxants require close monitoring for adverse effects, especially during initiation and dose adjustments 1, 7

In conclusion, based on the FDA label and available evidence, tizanidine should be avoided in patients with ESRD on hemodialysis with a GFR of 13. If muscle relaxation is necessary for back spasms, alternative agents with better safety profiles in renal impairment should be considered.