What is the appropriate dose of Polymyxin B for a 73-year-old male with severe renal impairment?

Polymyxin B Dosing in Severe Renal Impairment

For a 73-year-old male with severe renal impairment (creatinine 7 mg/dL), administer polymyxin B at the standard dose of 1.5-3 mg/kg/day in 2 divided doses with a loading dose of 2-2.5 mg/kg, without dose reduction for renal dysfunction. 1

Key Dosing Principle

Polymyxin B does NOT require dose adjustment for renal impairment because its plasma concentration is not influenced by renal function, unlike colistin. 1 This is a critical distinction from other antibiotics and represents a major advantage in patients with severe renal dysfunction.

Specific Dosing Regimen

Loading Dose

• Administer 2-2.5 mg/kg as a loading dose to achieve optimal plasma levels on the first day 1
• The loading dose should be given to ALL patients, including those with renal dysfunction 1

Maintenance Dose

• 1.5-3 mg/kg/day divided into 2 doses (every 12 hours) 1
• Continuous infusion may be suitable as an alternative 1
• The total daily dose must not exceed 25,000 units/kg/day per FDA labeling 2

Critical Pharmacokinetic Considerations

Polymyxin B clearance is calculated based on body weight, and renal function does not significantly affect its pharmacokinetics. 1 This has been confirmed by multiple studies:

• Research demonstrates comparable polymyxin B exposures (AUC) in patients with normal renal function versus renal insufficiency (63.5 vs 56.0 mg·h/L, P=0.42) 3
• Population pharmacokinetic studies show that while creatinine clearance is a covariate on clearance, the effect is modest, and standard dosing remains appropriate 4, 5

Renal Replacement Therapy Considerations

If the patient requires continuous renal replacement therapy (CRRT), dose adjustment is NOT necessary - use the same standard dose of 1.5-3 mg/kg/day. 1

Safety Profile in Renal Impairment

Polymyxin B has a lower incidence of nephrotoxicity compared to colistin, making it a preferable choice in patients with existing renal dysfunction. 1

Risk Factors for Nephrotoxicity to Monitor:

• Daily dose >1.5 mg/kg by actual body weight increases risk (HR=1.73) 6
• Concurrent vancomycin use (HR=1.89) 6
• Concurrent contrast media exposure (HR=1.79) 6
• Median onset of nephrotoxicity is 9 days if it occurs 6

Common Pitfalls to Avoid

Do NOT reduce the polymyxin B dose based on the FDA label's outdated recommendation that states "this amount should be reduced from 15,000 units/kg downward for individuals with kidney impairment." 2 This guidance contradicts current pharmacokinetic evidence showing renal function does not significantly affect polymyxin B clearance. 1, 3

Do NOT extrapolate colistin dosing principles to polymyxin B - colistin requires dose adjustment for renal function, but polymyxin B does not. 1

Practical Example for This Patient

Assuming a 70 kg actual body weight:

• Loading dose: 140-175 mg (2-2.5 mg/kg)
• Maintenance: 105-210 mg/day divided into 2 doses (1.5-3 mg/kg/day)
• No reduction needed despite creatinine of 7 mg/dL