How do you reconstitute amphotericin B (antifungal medication) liposomal?

From the Guidelines

To reconstitute liposomal amphotericin B (AmBisome), first allow the vial to reach room temperature, then add 12 mL of sterile water for injection to each 50 mg vial, creating a concentration of 4 mg/mL, as this method is crucial for maintaining the drug's efficacy and reducing nephrotoxicity 1. The reconstitution process is critical for the stability and effectiveness of the medication.

• Add 12 mL of sterile water for injection to each 50 mg vial,
• Do not use bacteriostatic water or saline solution,
• Shake the vial vigorously for at least 30 seconds until all material is completely dispersed. The reconstituted solution should be clear and yellow in color, and it is essential to inspect for particulate matter before proceeding with administration. For administration, further dilute the reconstituted solution with 5% dextrose injection to achieve the desired concentration, typically 0.2-0.5 mg/mL for peripheral administration or 0.2-2 mg/mL for central line administration, and use the diluted infusion within 6 hours if stored at room temperature or within 24 hours if refrigerated, as recommended in clinical practice guidelines 1. Proper reconstitution and administration are vital because liposomal formulations maintain the drug within lipid bilayers, which helps reduce nephrotoxicity while maintaining antifungal efficacy against invasive fungal infections. Key considerations include:
• Using sterile water for injection to prevent contamination,
• Avoiding bacteriostatic water or saline solution to maintain the drug's stability,
• Ensuring the solution is clear and free of particulate matter before administration,
• Diluting the solution correctly to achieve the desired concentration, and
• Using the diluted infusion within the recommended time frame to ensure efficacy and safety. By following these steps and guidelines, healthcare providers can effectively reconstitute and administer liposomal amphotericin B, minimizing the risk of adverse effects while maximizing its antifungal efficacy.

From the FDA Drug Label

Reconstitute as follows: An initial concentrate of 5 mg amphotericin B per mL is first prepared by rapidly expressing 10 mL Sterile Water for Injection USP without a bacteriostatic agent directly into the lyophilized cake, using a sterile needle (minimum diameter: 20 gauge) and syringe. Shake the vial immediately until the colloidal solution is clear. The infusion solution, providing 0. 1 mg amphotericin B per mL, is then obtained by further dilution (1:50) with 5% Dextrose Injection USP of pH above 4.2. To reconstitute amphotericin B liposomal, first prepare an initial concentrate of 5 mg amphotericin B per mL by adding 10 mL of Sterile Water for Injection USP to the lyophilized cake. Shake the vial until the solution is clear. Then, dilute the concentrate 1:50 with 5% Dextrose Injection USP to obtain the infusion solution, which provides 0.1 mg amphotericin B per mL. Use aseptic technique and do not reconstitute with saline solutions. 2

From the Research

Reconstituting Amphotericin B Liposomal

To reconstitute amphotericin B liposomal, it is essential to follow the guidelines provided by the manufacturer or established medical protocols.

• The reconstitution process typically involves adding a specified volume of sterile water to the amphotericin B liposomal powder to achieve the desired concentration.
• According to 3, when preparing intravenous admixtures of amphotericin B, it is crucial to store them at 4-8 degrees C, as commercial formulations lack a bacteriostatic agent.
• The choice of container for admixtures is also important, as certain materials may cause precipitation of amphotericin B.
• It is recommended to begin intravenous therapy with a 1-mg test dose, as suggested by the manufacturer, to assess patient tolerance.

Administration Considerations

When administering amphotericin B liposomal, consider the following:

• The usual daily maintenance dose is 0.5-1 mg/kg i.v., as stated in 3.
• Amphotericin B can be infused over one to two hours (less than or equal to 50 mg/hr) in patients with adequate renal function.
• Patients with a history of hypersensitivity or unacceptable reactions may require prophylactic ancillary medications to mitigate infusion-related adverse events.

Stability and Storage

• The stability of reconstituted amphotericin B liposomal solutions is critical for maintaining efficacy and safety.
• As noted in 3, intravenous admixtures of amphotericin B have specific expiration dates, depending on the concentration and storage conditions.
• It is essential to follow the recommended storage guidelines to ensure the stability of the reconstituted solution.

Lipid Formulations

• The development of lipid-based formulations of amphotericin B, such as liposomal amphotericin B, has aimed to reduce the toxic potential of the conventional drug, as discussed in 4.
• These formulations have distinct characteristics that may influence therapeutic results, highlighting the need for careful consideration when selecting a formulation for treatment.