What is the recommended dose of Polymyxin B (Polymyxin B) for patients with Chronic Kidney Disease (CKD) and Impaired Renal Function?

Polymyxin B Dosing in Chronic Kidney Disease

Polymyxin B does NOT require dose adjustment in patients with CKD, as renal function does not significantly influence its plasma concentrations or clearance. This represents a critical departure from the outdated FDA labeling and stands in direct contrast to colistin (polymyxin E), which does require renal dose adjustment 1.

Key Dosing Recommendations

Standard Dosing Regardless of Renal Function

• Administer 1.5-3 mg/kg/day based on actual body weight, divided into twice-daily dosing 1
• Always use a loading dose of 2-2.5 mg/kg to achieve optimal plasma levels on day one, regardless of renal function 1
• No dose reduction is necessary for patients with renal insufficiency or those on continuous renal replacement therapy (CRRT) 1

Critical Evidence Supporting No Dose Adjustment

The most recent high-quality research directly contradicts the FDA label:

• A 2017 pharmacokinetic study demonstrated that polymyxin B exposures (AUC) were comparable between patients with normal renal function (63.5 ± 16.6 mg·h/L) versus renal insufficiency (56.0 ± 17.5 mg·h/L), with no statistical difference (P = 0.42) 2
• A 2021 population pharmacokinetic study found that while creatinine clearance was a covariate on clearance, the actual clinical impact was minimal, and dose reduction in renal insufficiency actually improved the probability of achieving optimal exposure 3
• The 2015 Intensive Care Medicine guidelines explicitly state that polymyxin B plasma concentrations are not influenced by renal function, unlike colistin 1

Dosing Algorithm by Clinical Scenario

Patients with CKD (Not on Dialysis)

• Loading dose: 2-2.5 mg/kg actual body weight 1
• Maintenance: 1.5-3 mg/kg/day divided every 12 hours 1
• No adjustment needed regardless of creatinine clearance 1

Patients on Continuous Renal Replacement Therapy (CRRT)

• Use the same dosing as patients with normal renal function 1
• Loading dose: 2-2.5 mg/kg 1
• Maintenance: 1.5-3 mg/kg/day divided every 12 hours 1
• No dose adjustment necessary 1

Patients on Intermittent Hemodialysis

• Administer after dialysis to avoid premature drug removal 4, 5
• Use standard dosing: 1.5-3 mg/kg/day divided every 12 hours 1

Dosing Frequency: Twice Daily is Superior

Administer polymyxin B twice daily rather than once daily to minimize nephrotoxicity risk:

• A 2018 multicenter study found that once-daily dosing resulted in significantly higher nephrotoxicity rates (47%) compared to twice-daily dosing (17%), with an adjusted odds ratio of 2.5 (P = 0.002) 6
• Twice-daily administration maintains efficacy while reducing the risk of acute kidney injury 6

Nephrotoxicity Risk Factors to Monitor

While dose adjustment isn't needed for CKD, be vigilant about nephrotoxicity risk factors:

• Daily dose >1.5 mg/kg actual body weight increases nephrotoxicity risk (HR = 1.73) 7
• Concurrent vancomycin use increases risk (HR = 1.89) 7
• Concurrent contrast media increases risk (HR = 1.79) 7
• Higher BMI independently predicts acute kidney injury 8
• Median onset of nephrotoxicity is 7-9 days after starting therapy 6, 7

Critical Pitfalls to Avoid

Do Not Follow the Outdated FDA Label

• The FDA label recommends reducing polymyxin B dose "from 15,000 units/kg downward for individuals with kidney impairment," but this recommendation is not supported by modern pharmacokinetic data 9
• This outdated guidance predates the understanding that polymyxin B clearance is primarily non-renal 1, 2

Do Not Confuse Polymyxin B with Colistin

• Colistin (polymyxin E) DOES require dose adjustment for renal function because it is administered as an inactive prodrug (colistimethate sodium) that is renally cleared 1
• Polymyxin B is administered as the active drug and is NOT primarily renally cleared 1

Do Not Use Once-Daily Dosing

• Once-daily dosing significantly increases nephrotoxicity risk without improving efficacy 6
• Always divide the total daily dose into twice-daily administration 1, 6

Do Not Skip the Loading Dose

• Without a loading dose, therapeutic concentrations are delayed by 2-3 days, potentially compromising outcomes in critically ill patients 1

Monitoring Requirements

• Baseline serum creatinine and ongoing renal function monitoring every 2-3 days during therapy 7, 8
• Assess for concurrent nephrotoxins (vancomycin, contrast media, NSAIDs) and minimize when possible 7, 8
• Consider therapeutic drug monitoring in critically ill patients, though specific polymyxin B targets are not yet well-established 3
• Monitor for clinical response and adjust duration based on infection severity, typically 7-14 days 7, 8