Polymyxin B Dosing in Patients with Impaired Renal Function
Polymyxin B does NOT require dose adjustment for renal impairment—use the standard dose of 1.5-3 mg/kg/day divided into 2 doses with a loading dose of 2-2.5 mg/kg, regardless of creatinine clearance. 1, 2
Critical Pharmacokinetic Principle
The fundamental difference between polymyxin B and colistin is that polymyxin B plasma concentrations are not influenced by renal function because dosing is calculated based on body weight and the drug undergoes minimal renal elimination. 1, 2 This is in stark contrast to colistin (colistimethate sodium), which requires dose adjustment in renal impairment. 1
Standard Dosing Regimen for All Renal Functions
Loading Dose
- Administer 2-2.5 mg/kg as a loading dose on day 1 to rapidly achieve therapeutic plasma levels. 1, 2
- The loading dose must be given to ALL patients, including those with severe renal dysfunction. 1, 2
Maintenance Dose
- 1.5-3 mg/kg/day divided into 2 doses (typically every 12 hours). 1, 2
- For severe infections (e.g., VAP, bloodstream infections): 2.5-3 mg/kg/day divided in 2 daily IV doses. 1, 3
- Continuous infusion may be suitable as an alternative administration method. 1
Practical Dosing Example
For a 70 kg patient with severe renal impairment:
- Loading dose: 140-175 mg (2-2.5 mg/kg)
- Maintenance dose: 105-210 mg/day divided into 2 doses (52.5-105 mg every 12 hours)
- No reduction needed despite renal dysfunction. 2
Renal Replacement Therapy Considerations
Patients on continuous renal replacement therapy (CRRT) require NO dose adjustment—use the same standard dose of 1.5-3 mg/kg/day. 1, 2, 3 This is a major advantage over colistin, which requires complex dosing adjustments during dialysis. 4
Critical Caveats and Pitfalls
FDA Label Discrepancy
The FDA-approved prescribing information states that polymyxin B "should be reduced from 15,000 units/kg downward for individuals with kidney impairment" (equivalent to reducing from 1.5 mg/kg/day). 5 However, this recommendation contradicts current pharmacokinetic evidence and expert guidelines. Multiple studies demonstrate poor correlation between creatinine clearance and polymyxin B clearance. 6, 7
Recent Evidence Challenging Traditional Dosing
- A 2017 study found no significant difference in polymyxin B exposure between patients with normal renal function (AUC 63.5 mg·h/L) versus renal insufficiency (AUC 56.0 mg·h/L, P=0.42). 7
- A 2021 population pharmacokinetic study identified creatinine clearance as a significant covariate on clearance, suggesting dose reduction in renal insufficiency may improve the probability of achieving optimal exposure while reducing nephrotoxicity risk. 6
Resolving the Contradiction
The weight of current guideline evidence (2015-2025) supports NO dose adjustment for renal impairment. 1, 2 The 2021 research suggesting dose reduction 6 is outweighed by:
- Multiple international ICU guidelines recommending standard dosing 1
- The 2017 study showing equivalent exposures 7
- The pharmacokinetic principle that polymyxin B is not renally eliminated 1, 2
In clinical practice, use standard dosing without renal adjustment, but monitor closely for nephrotoxicity.
Safety Considerations
- Polymyxin B has lower nephrotoxicity compared to colistin, making it preferable in patients with existing renal dysfunction. 2, 4
- Avoid concurrent nephrotoxic agents, particularly the combination of NSAIDs, diuretics, and ACE inhibitors/ARBs. 3
- For infections with MIC ≥2 mg/L, high doses increase bacterial eradication but also increase nephrotoxicity risk. 6, 8
- Consider therapeutic drug monitoring where available to optimize dosing. 3
Body Weight Considerations
Patient weight significantly influences exposure. 8 For critically ill patients:
- 50 kg patients: May require 2 mg/kg q12h
- 75 kg patients: May require 1.25 mg/kg q12h
- 100 kg patients: May require 1 mg/kg q12h
This suggests heavier patients may need lower per-kilogram doses to avoid toxicity while maintaining efficacy. 8