What is the recommended dose of Polymyxin B for a patient with normal renal function?

Polymyxin B Dosing in Normal Renal Function

For patients with normal renal function, administer polymyxin B as a loading dose of 2-2.5 mg/kg followed by maintenance dosing of 1.5-3 mg/kg/day divided into two doses every 12 hours, with no dose reduction required for any degree of renal impairment. 1

Loading Dose Protocol

• Always initiate therapy with a loading dose of 2-2.5 mg/kg to rapidly achieve therapeutic plasma concentrations on the first day, regardless of renal function status 1, 2
• The loading dose is critical for achieving optimal plasma levels immediately and must be given to all patients, including those with severe renal dysfunction or on continuous renal replacement therapy (CRRT) 1, 2
• For a 70 kg patient with normal renal function, this translates to a loading dose of 140-175 mg 2

Maintenance Dosing

• Administer 1.5-3 mg/kg/day divided into two doses (every 12 hours) as the standard maintenance regimen 1, 2
• For a 70 kg patient, the maintenance dose is 105-210 mg/day divided into two doses 1
• The FDA label states 15,000-25,000 units/kg/day (equivalent to 1.5-2.5 mg/kg/day), but current guidelines recommend up to 3 mg/kg/day based on therapeutic drug monitoring data 3, 1

Critical Distinction from Older FDA Labeling

• The most important clinical point is that polymyxin B does NOT require dose adjustment for renal impairment, which directly contradicts older FDA labeling that recommended dose reduction 1, 2
• This is the key distinction from colistin, which does require renal dose adjustment 4
• Polymyxin B clearance is not significantly influenced by renal function, as its elimination is predominantly non-renal with only 4% urinary recovery 5

Evidence Supporting No Renal Adjustment

The guideline recommendations are strongly supported by pharmacokinetic research:

• A 2017 study showed 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) 6
• A 2013 population pharmacokinetic study in critically ill patients demonstrated that polymyxin B clearance showed no relationship with creatinine clearance (r²=0.008) 5

However, there is contradictory evidence: A 2021 study and a 2023 study both found that renal function does affect polymyxin B clearance, with patients having renal insufficiency showing significantly lower clearance and higher AUC values 7, 8. The 2023 study showed AUC of 87 mg·h/L in renal insufficiency versus 67.8 mg·h/L in normal function, and recommended dose reduction in renal insufficiency 8.

Despite this conflicting research, the most recent guidelines (2026) from the American College of Clinical Pharmacology and Intensive Care Society definitively recommend no dose adjustment for renal impairment 1, 2. This guideline-based approach should take precedence in clinical practice.

Therapeutic Drug Monitoring

• Target a steady-state average concentration of approximately 3.35 mg/L 1, 2
• Optimal AUCss,24h target is 50-100 mg·h/L 1
• Therapeutic drug monitoring is strongly encouraged to optimize dosing and minimize toxicity, particularly given the conflicting pharmacokinetic data 1, 2

Nephrotoxicity Considerations

• Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%) 1, 4
• Avoid concurrent nephrotoxic agents such as aminoglycosides, NSAIDs, diuretics, and ACE inhibitors/ARBs 2
• Monitor renal function closely during therapy 4

Combination Therapy Requirements

• Use polymyxin B in combination therapy rather than monotherapy for carbapenem-resistant infections 1
• For ventilator-associated pneumonia (VAP) or hospital-acquired pneumonia (HAP) caused by carbapenem-resistant pathogens sensitive only to polymyxins, combine intravenous polymyxin B with adjunctive inhaled colistin (not inhaled polymyxin B) 1
• Consider combination with tigecycline or meropenem (extended infusion) for carbapenem-resistant Enterobacterales bloodstream infections 1

Common Pitfalls to Avoid

• Do not reduce the dose based on renal function - this is the most common error based on outdated FDA labeling 1, 2
• Do not skip the loading dose - failure to give a loading dose delays achievement of therapeutic concentrations 1
• Do not use polymyxin B as monotherapy for serious infections - combination therapy is recommended 1