Does Amphotericin B (antifungal medication) need to be diluted before injection?

Amphotericin B Must Be Diluted Before Intravenous Administration

Yes, amphotericin B injection absolutely requires dilution before administration—this is a non-negotiable requirement for safe intravenous use. The lyophilized powder must first be reconstituted with sterile water, then further diluted in 5% dextrose solution before infusion 1.

Reconstitution and Dilution Protocol

Initial Reconstitution

• Reconstitute the lyophilized cake by adding 10 mL of Sterile Water for Injection (without bacteriostatic agents) directly to the vial to create an initial concentrate of 5 mg/mL 1
• Use a sterile needle with minimum 20-gauge diameter and shake immediately until the colloidal solution is clear 1
• This concentrated solution cannot be administered directly and requires further dilution 1

Final Dilution for Infusion

• The reconstituted concentrate must be further diluted 1:50 with 5% Dextrose Injection to achieve a final concentration of 0.1 mg/mL (1 mg per 10 mL) 1
• The pH of the dextrose solution must be above 4.2 before use; if below 4.2, add 1-2 mL of phosphate buffer 1
• Alternative concentrations of 0.25-1.4 mg/mL in 5% dextrose can be used depending on clinical needs 2

Critical Safety Considerations

What NOT to Use

• Never reconstitute or dilute with saline solutions—this will cause precipitation of the drug 1
• Do not use any diluent containing bacteriostatic agents (e.g., benzyl alcohol) as this causes precipitation 1
• Avoid any dextrose solution with pH below 4.2 unless buffered appropriately 1

Aseptic Technique Requirements

• Strict aseptic technique is mandatory throughout preparation since no preservative is present 1
• All entries into vials or diluents must use sterile needles 1
• Discard any solution showing evidence of precipitation or foreign matter 1

Administration Parameters

Infusion Rate and Duration

• Infuse over 2-6 hours for conventional amphotericin B deoxycholate, with typical infusions lasting 1-2 hours in patients with adequate renal function 3, 1
• Infusion rate should not exceed 50 mg/hour 2
• Liposomal formulations typically infuse over 2 hours (minimum 1 hour) 3
• Patients with azotemia or hyperkalemia require longer infusion times of 3-6 hours to reduce toxicity 4

Pre-medication and Hydration

• Administer 1 L of normal saline 30 minutes before amphotericin B infusion to reduce nephrotoxicity in patients who can tolerate fluids 5, 4
• Pre-medicate with diphenhydramine or acetaminophen to reduce infusion-related reactions (fever, chills, rigors) 5, 3
• Consider prophylactic meperidine for patients with history of severe rigors 6

Filtration Considerations

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

Storage of Diluted Solutions

• Admixtures of amphotericin B 0.25 mg/mL in 5% dextrose have a 35-day expiration when stored at 4-8°C 2
• Higher concentrations (1.4 mg/mL) have only 36-hour stability 2
• Protection from fluorescent light is unnecessary 2
• Store in polyolefin, glass, or polyvinyl chloride containers; avoid evacuated containers with buffers 2

Common Pitfalls to Avoid

• Using saline as a diluent is the most common error and results in immediate precipitation 1
• Failing to check dextrose pH before dilution can lead to drug precipitation 1
• Administering the initial 5 mg/mL concentrate without further dilution causes severe toxicity 1
• Using filters with pore size less than 1.0 micron blocks drug passage 1