Dosing of polymyxin B in Haemodialysis

Availability: Colomycin/ Colistimethate sodium 1-2 million IU
Dose Conversion

• 1 mg colistin BASE activity (CBA) = 2.4 mg colistimethate sodium 
• 1 mg colistin BASE activity (CBA) = 30,000 IU 
• 1 mg colistimethate sodium (CMS) = 12,500 IU

Dosing Considerations:

• Best practices for colistin dosing are unclear
• Dosing of colistin in hemodialysis patients has varied in published reports
• manufacturer does not provide dosing recommendations for hemodialysis patients or for peritoneal dialysis patients
• intermittent hemodialysis removed a significant quantity of colistin and colistimethate

Dosing Recommendations: 
1. http://www.asp.mednet.ucla.edu/files/view/guidebook/Colistin_Dosing

• High-dose CBA (optimizes the concentration-dependent bactericidal activity). 
• loading dose is included to ensure that therapeutic concentrations are rapidly achieved. 
• In the absence of a loading dose, it may take 48 hours before colistin concentrations exceed the bacterial minimum inhibitory concentration

OR

2. http://www.nebraskamed.com/careers/education-programs/asp/restrictions/colistin

• Maintenance dose and dosing interval should be based on the renal dosing protocol
• A load of 2.5 mg/kg IV q12h x2doses should be given to all patients with a creatinine clearance (CrCl) of <= 40 ml/min (the loading doses are not renally adjusted)
• Subsequent maintenances doses should begin 24 hours after the first loading dose
• In pediatric patients use 1.5 mg/kg/day divided q12h

CrCl >40: No adjustment necessary
CrCl 20-40: 75% of total daily dose IV divided q12h
CrCl 10-19: 50% of total daily dose IV divided q12h
CrCl <10, intermittent hemodialysis, or peritoneal dialysis: 50 mg IV q12h. Administered after dialysis on dialysis days

 OR

3. http://www.infectiousdiseases-ucla-affiliated.org/Intranet/FILES/ColistinDosing

Loading dose 

• (LD, All patient categories) LD of CBA (mg) =5.0 x body wt (kg) 
• Use the lower of ideal or actual body wt (kg) 
• Not to exceed 300mg 

Maintenance dose: 

• 1 st dose should be given 24 hours after LD 
• Not on renal replacement therapy: Daily dose of CBA (mg) = 2.5 x (1.5xCrcl+30)
• Dosing interval adjusted based on CrCl (ml/min/1.73m2): 
• CrCl70ml/min/1.73m2 = q8h 

Intermittent hemodialysis: 

• None HD day- Daily dose of CBA = 75mg; given as 37.5 mg q 12h 
• On days when dialysis is given an additional 30% of the daily maintenance dose is given after HD [exm: 1 st dose = 37.5mg. Second dose (12 hours later) = 60 mg ]

CRRT: 

• Daily dose =480mg; give as 160 mg q 8 h.

OR

4. Medscape

•  intravenous dosages of CMS are 2–3 mg/kg after each hemodialysis treatment

Suggestion:

• Based on available guides, do suggest to use a BD dosing to achieve therapeutic level
• (case report:  patient received 2 million units of colistimethate every 12 hours, and received hemodialysis on a daily basis. Patient achieved close to the MIC breakpoint of 2 mg/L)
• As most recommendations are at a lower dosing, would suggest for initiation at 1-1.5 million Unit BD rather than 2 million unit. 

References:

1. http://www.ahcmedia.com/articles/20230-colistin-dosing-in-renally-impaired-patients
2. http://www.asp.mednet.ucla.edu/files/view/guidebook/Colistin_Dosing
3. http://www.nebraskamed.com/careers/education-programs/asp/restrictions/colistin
4. http://www.infectiousdiseases-ucla-affiliated.org/Intranet/FILES/ColistinDosing
5. https://www.medicines.org.uk/EMC/medicine/1590/SPC/Colomycin+Injection/
6. http://www.medscape.com/viewarticle/772588_4
7. http://ac.els-cdn.com/S120197121401666X/1-s2.0-S120197121401666X-main