Maximum Dose of Polymyxin B
The maximum recommended daily dose of polymyxin B is 3 mg/kg/day (or approximately 200-210 mg/day for a 70 kg patient), divided into two doses given every 12 hours, preceded by a loading dose of 2-2.5 mg/kg. 1, 2, 3
Standard Dosing Protocol
Loading Dose:
- Administer 2-2.5 mg/kg as a loading dose to all patients, regardless of renal function status 1, 2, 3
- This loading dose is critical to rapidly achieve therapeutic plasma concentrations on the first day 2
- Never omit the loading dose, even in patients with severe renal dysfunction or on continuous renal replacement therapy (CRRT) 2
Maintenance Dosing:
- The maintenance dose range is 1.5-3 mg/kg/day divided into two doses (every 12 hours) 1, 2, 3
- For a 70 kg patient, this translates to 105-210 mg/day total 2
- The upper limit of 3 mg/kg/day represents the maximum recommended dose 3
Critical Dosing Considerations
Renal Function:
- Do NOT reduce the dose in patients with renal impairment - this is the most important distinction from colistin and contradicts older FDA labeling 2, 4
- Polymyxin B clearance is not significantly influenced by renal function, unlike colistin 1, 4, 5
- No dose adjustment is necessary for patients on CRRT 1, 2, 4
FDA Label Discrepancy:
- The FDA label recommends a maximum of 25,000 units/kg/day (equivalent to 2.5 mg/kg/day, since 1 mg = 10,000 units) and suggests dose reduction in renal impairment 6
- However, current clinical evidence and guidelines contradict this recommendation, showing that renal function does not significantly affect polymyxin B pharmacokinetics 2, 4, 5
- Follow the guideline-based dosing (up to 3 mg/kg/day) rather than the outdated FDA label 1, 2
Therapeutic Drug Monitoring
Target Concentrations:
- Target steady-state average concentration (Css,avg) of approximately 3.35 mg/L 2, 7
- Optimal AUCss,24h target is 50-100 mg·h/L 2
- Therapeutic drug monitoring is strongly encouraged to optimize dosing and minimize toxicity 1, 2
Safety Considerations
Nephrotoxicity Risk:
- Polymyxin B has significantly lower nephrotoxicity compared to colistin (11.8% vs 39.3%) 2, 4, 3
- Avoid concurrent nephrotoxic agents including aminoglycosides, NSAIDs, diuretics, and ACE inhibitors/ARBs 3
- Monitor renal function closely during therapy 1, 4
Maximum Dose Limitations:
- While 3 mg/kg/day is the recommended maximum, doses as high as 45,000 units/kg/day (4.5 mg/kg/day) have been used in limited studies in premature and newborn infants 6
- For severe infections with organisms having MIC ≥2 mg/L, higher doses may be considered but carry increased nephrotoxicity risk 8
- Monte Carlo simulations suggest that even maximum doses may have inadequate probability of target attainment for MIC ≥2 mg/L 7
Combination Therapy Requirement
- Polymyxin B should always be used in combination therapy, not as monotherapy, for carbapenem-resistant infections 1, 2, 3
- Combine with antipseudomonal β-lactams (piperacillin-tazobactam, cefepime, or meropenem) for ventilator-associated pneumonia 3
- Consider combination with tigecycline or extended-infusion meropenem for carbapenem-resistant Enterobacterales bloodstream infections 2
Common Pitfalls to Avoid
- Do not confuse polymyxin B with colistin dosing - they have completely different unit conversions and dosing requirements (polymyxin B: 1 mg = 10,000 units; colistin: 1 million IU = 80 mg CMS = 33 mg CBA) 1
- Do not reduce doses based on renal function - this outdated practice leads to subtherapeutic levels 2, 4
- Do not skip the loading dose - failure to load results in subtherapeutic levels for the first 24-48 hours 2