How to dilute intravenous (IV) amphotericin B?

How to Dilute Intravenous Amphotericin B

Amphotericin B deoxycholate must be reconstituted with 10 mL sterile water for injection (without bacteriostatic agents) to create a 5 mg/mL concentrate, then diluted 1:50 in 5% dextrose (D5W) with pH >4.2 to achieve a final concentration of 0.1 mg/mL for infusion. 1

Reconstitution Protocol

Initial Concentrate Preparation

• Rapidly inject 10 mL of Sterile Water for Injection USP (without bacteriostatic agents) directly into the lyophilized cake using a sterile needle with minimum 20-gauge diameter 1
• Shake the vial immediately until the colloidal solution is completely clear 1
• This creates an initial concentrate of 5 mg amphotericin B per mL 1

Final Dilution for Infusion

• Dilute the concentrate 1:50 with 5% Dextrose Injection (D5W) to obtain a final concentration of 0.1 mg amphotericin B per mL 1
• The pH of the D5W must be above 4.2 before use 1
• If the D5W pH is below 4.2, add 1-2 mL of phosphate buffer before diluting the amphotericin B concentrate 1

Critical Preparation Requirements

What NOT to Use

• Never reconstitute with saline solutions—this will cause precipitation 1
• Do not use any diluent containing bacteriostatic agents (e.g., benzyl alcohol) as this causes precipitation 1
• Do not use D5W or any diluent other than those specifically recommended 1

Volume Considerations

• For 25 mg amphotericin B: use 250 mL D5W (not 500 mL) 2
• For 50 mg amphotericin B: use 500 mL D5W 2
• Using 25 mg in 500 mL creates excessive insoluble particles (>10 μm) that exceed pharmacopeial limits and can cause filter blockage 2
• The 25 mg/500 mL preparation resulted in only 11.3% of drug flowing through after 6 hours due to filter obstruction 2

Aseptic Technique Requirements

• Strict aseptic technique must be observed throughout all handling 1
• No preservative or bacteriostatic agent is present in the formulation 1
• All entries into the vial or diluents must be made with a sterile needle 1
• Do not use if there is any evidence of precipitation or foreign matter in either the concentrate or final infusion solution 1

Filtration Considerations

• An in-line membrane filter may be used during infusion 1
• The mean pore diameter must not be less than 1.0 micron to ensure passage of the antibiotic dispersion 1

Alternative Lipid Emulsion Formulation

While the FDA-approved method uses D5W, research demonstrates that amphotericin B can be mixed with 20% Intralipid (fat emulsion) as an alternative that may reduce toxicity 3, 4:

• Dilute amphotericin B in 20% Intralipid at 1 mg/kg body weight 3
• This formulation reduces acute infusion reactions (fever in 23% vs 40% with D5W) 3
• Significantly fewer cases of hypokalemia occur with lipid emulsion (P=0.004) 3, 4
• Nephrotoxicity is reduced compared to conventional D5W preparation 4
• However, this is an off-label preparation method and pharmacokinetics differ significantly from standard formulation 5

Pre-Infusion Requirements

• Administer 1 L of normal saline 30 minutes before amphotericin B infusion in patients who can tolerate fluids 6, 7
• Premedicate with diphenhydramine or acetaminophen to reduce infusion-related reactions 6, 7

Common Pitfalls to Avoid

• Using 25 mg in 500 mL D5W (causes filter blockage and incomplete drug delivery) 2
• Failing to verify D5W pH is >4.2 before dilution (causes precipitation) 1
• Using saline or bacteriostatic water (causes immediate precipitation) 1
• Breaking aseptic technique (no preservatives present to prevent contamination) 1
• Using filters <1.0 micron pore size (blocks drug passage) 1