What is the recommended dosage of Polymixin B (Polymyxin B) for a patient with impaired renal function?

Polymyxin B Dosing in Renal Impairment

Polymyxin B does not require dose reduction in patients with impaired renal function—use the standard loading dose of 2-2.5 mg/kg followed by maintenance dosing of 1.5-3 mg/kg/day divided into 2 doses, regardless of creatinine clearance. 1, 2

Loading Dose (All Patients)

• Administer 2-2.5 mg/kg as a loading dose to all patients, including those with severe renal dysfunction 1, 2
• This loading dose is critical to rapidly achieve therapeutic plasma concentrations on day 1 2
• For a 70 kg patient, this translates to 140-175 mg as the initial dose 2

Maintenance Dosing

Standard regimen regardless of renal function:

• 1.5-3 mg/kg/day divided into 2 doses (every 12 hours) 1, 2
• For a 70 kg patient: 105-210 mg/day in 2 divided doses 2
• Do not reduce this dose in renal impairment 2, 3

Key Pharmacokinetic Rationale

Why no dose adjustment is needed:

• Polymyxin B clearance is calculated based on body weight, not renal function 2
• Plasma concentrations are not influenced by renal function, unlike colistin 1, 2
• Studies show comparable drug exposures (AUC 63.5 vs 56.0 mg·h/L) in patients with normal versus impaired renal function receiving standard dosing 4

Continuous Renal Replacement Therapy (CRRT)

• Use the same standard dose of 1.5-3 mg/kg/day—no adjustment necessary 1, 2
• A fixed maintenance dose of 100 mg every 12 hours after a 200 mg loading dose is optimal for patients on CVVHD 5

Critical Distinction from FDA Labeling

Important contradiction to address:

• The FDA label recommends dose reduction from 15,000-25,000 units/kg/day downward in renal impairment 6
• However, current pharmacokinetic evidence and international guidelines contradict this outdated recommendation 2, 3
• Multiple studies demonstrate poor correlation between creatinine clearance and polymyxin B clearance 7, 4
• Modern guidelines from the Intensive Care Society explicitly state no dose adjustment is needed 1, 2

Nephrotoxicity Risk Management

Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%) 3

To minimize nephrotoxicity risk:

• Avoid concurrent nephrotoxic agents: aminoglycosides, NSAIDs, diuretics, ACE inhibitors/ARBs 2, 3
• Consider therapeutic drug monitoring with target steady-state concentration of approximately 3.35 mg/L 2, 3

Nuanced Evidence on Renal Function Impact

Emerging data suggests some dose adjustment may be beneficial:

• Recent population PK studies show creatinine clearance does significantly affect polymyxin B clearance 7, 8
• Patients with renal insufficiency demonstrate lower clearance (2.1 L/h vs 3.9 L/h in normal function) 5
• One study suggests dose reduction in renal insufficiency improves probability of achieving optimal exposure while reducing nephrotoxicity risk 7

However, the consensus guideline recommendation remains no dose adjustment 1, 2, as the clinical significance of these PK differences has not been definitively established in outcomes studies.

Common Pitfalls to Avoid

• Do not confuse polymyxin B with colistin dosing—they have completely different pharmacokinetics and unit conversions 3
• Do not omit the loading dose—this results in subtherapeutic levels for 24-48 hours 3
• Do not use as monotherapy for carbapenem-resistant infections when combination therapy is feasible 3
• Do not follow the outdated FDA label recommending dose reduction in renal impairment 2, 3

Practical Dosing Example

For a 70 kg patient with severe renal impairment (CrCL <30 mL/min):

• Day 1: Loading dose of 175 mg (2.5 mg/kg)
• Maintenance: 105 mg every 12 hours (1.5 mg/kg/day)
• No reduction despite severe renal dysfunction 2