Colistin Loading Dose Dilution
For colistin loading dose administration, reconstitute each 150 mg vial with 2 mL of Sterile Water for Injection to achieve a concentration of 75 mg/mL colistin base activity, then dilute the required loading dose (6-9 million IU) in 50-150 mL of compatible IV solution (0.9% NaCl, 5% dextrose in water, or other FDA-approved solutions) and infuse over 3-5 minutes for direct administration or over 4 hours for optimized pharmacokinetics. 1, 2, 3
Reconstitution and Dilution Steps
Initial Reconstitution
- Add 2 mL Sterile Water for Injection to each 150 mg vial 1
- Swirl gently to avoid frothing; do not shake vigorously 1
- Final concentration after reconstitution: 75 mg/mL colistin base activity 1
- Inspect visually for particulate matter and discoloration before use 1
Loading Dose Preparation
- Loading dose requirement: 6-9 million IU regardless of renal function 4, 2, 3
- This loading dose is critical because colistin has a relatively long half-life compared to dosing intervals, and plasma concentrations remain sub-optimal for 2-3 days without loading 4
- Convert million IU to mg: 1 million IU = 80 mg colistimethate sodium (CMS) 5, 2
Final Dilution for Administration
- Compatible IV solutions include 1:
- 0.9% NaCl
- 5% dextrose in 0.9% NaCl
- 5% dextrose in water
- 5% dextrose in 0.45% NaCl
- 5% dextrose in 0.225% NaCl
- Lactated Ringer's solution
- 10% invert sugar solution
Administration Methods
Direct Intermittent Administration
- Inject the loading dose slowly over 3-5 minutes 1
- This rapid administration achieves therapeutic levels quickly 4
Optimized Infusion (Preferred)
- A 4-hour infusion is suggested to optimize pharmacokinetic/pharmacodynamic properties 2, 3
- This extended infusion may provide better drug exposure while minimizing concentration-related adverse effects 6
Critical Considerations for Renal Impairment
Loading Dose in Renal Impairment
- The loading dose of 6-9 million IU should NOT be adjusted for renal function 4, 2, 3
- This applies to all patients including those with severe renal impairment, on continuous renal replacement therapy (CRRT), or intermittent hemodialysis 2
- The rationale: loading dose achieves rapid therapeutic levels regardless of elimination capacity 4
Maintenance Dose Adjustments (Post-Loading)
For patients with renal impairment, maintenance doses require adjustment 2, 1:
- Normal renal function (CrCl ≥80 mL/min): 4.5 million IU every 12 hours 4, 2
- Mild impairment (CrCl 50-79 mL/min): 2.5-3.8 mg/kg divided into 2 doses 1
- Moderate impairment (CrCl 30-49 mL/min): 2.5 mg/kg once daily or divided into 2 doses 1
- Severe impairment (CrCl 10-29 mL/min): 1.5 mg/kg every 36 hours 1
- CRRT: At least 9 million IU/day total 4, 2
- Intermittent hemodialysis: 2 million IU every 12 hours with normal loading dose; schedule dialysis toward end of dosing interval 4, 2
Stability and Storage
- Freshly prepared IV infusion solutions containing colistimethate should be used within 24 hours 1
- Reconstituted solution for intramuscular use can be stored refrigerated at 2-8°C or at room temperature 20-25°C for up to 7 days 1
Common Pitfalls to Avoid
Do Not Reduce Loading Dose for Renal Impairment
- A critical error is reducing the loading dose in patients with renal dysfunction 2, 3
- Colistin is administered as inactive prodrug CMS, which converts slowly to active colistin 6
- Without adequate loading, therapeutic levels may not be achieved for 2-3 days, risking treatment failure 4
Monitor for Nephrotoxicity
- Colistin causes nephrotoxicity in approximately 39.3% of patients (compared to 11.8% with polymyxin B) 5
- Acute kidney injury during treatment is a major factor related to clinical failure and mortality 5, 3
- Close renal function monitoring is mandatory throughout therapy 2, 3