What is the recommended reconstitution and dosing for Amphotericin B (antifungal medication) in a patient requiring treatment for a fungal infection?

Amphotericin B Reconstitution and Administration

Reconstitute conventional amphotericin B by rapidly adding 10 mL of Sterile Water for Injection (without bacteriostatic agents) directly into the lyophilized vial to create an initial concentrate of 5 mg/mL, then dilute 1:50 with 5% Dextrose Injection (pH >4.2) to achieve a final concentration of 0.1 mg/mL for intravenous infusion. 1

Reconstitution Protocol for Conventional Amphotericin B

Initial Reconstitution

• Use a sterile needle with minimum diameter of 20 gauge and syringe to inject 10 mL Sterile Water for Injection USP directly into the lyophilized cake 1
• Shake the vial immediately until the colloidal solution is clear 1
• This creates an initial concentrate of 5 mg amphotericin B per mL 1

Final Dilution

• Further dilute the concentrate 1:50 with 5% Dextrose Injection USP to obtain 0.1 mg/mL (1 mg per 10 mL) 1
• Critical: The pH of the dextrose solution must be above 4.2 1
• If pH is below 4.2, add 1-2 mL of phosphate buffer (containing 1.59 g dibasic sodium phosphate and 0.96 g monobasic sodium phosphate per 100 mL water) before dilution 1

Important Reconstitution Warnings

• Never use saline solutions for reconstitution or dilution - this will cause precipitation 1
• Never use diluents containing bacteriostatic agents (e.g., benzyl alcohol) - this will cause precipitation 1
• Strict aseptic technique is mandatory as no preservative is present 1
• Do not use if any precipitation or foreign matter is visible 1

Dosing Recommendations

Test Dose

• Administer 1 mg in 20 mL of 5% dextrose over 20-30 minutes 1
• Monitor temperature, pulse, respiration, and blood pressure every 30 minutes for 2-4 hours 1

Standard Dosing for Conventional Amphotericin B Deoxycholate

For patients with good cardio-renal function and well-tolerated test dose:

• Initial dose: 0.25 mg/kg/day IV 1
• For severe, rapidly progressive infections: 0.3 mg/kg/day initially 1
• Gradually increase by 5-10 mg per day to reach final daily dose of 0.5-0.7 mg/kg 1, 2
• For life-threatening infections or less susceptible species: up to 1.0-1.5 mg/kg/day 1, 2, 3

For patients with impaired cardio-renal function or severe test dose reaction:

• Start with 5-10 mg daily 1
• Gradually increase by 5-10 mg per day as tolerated 1

Lipid Formulation Dosing

Liposomal Amphotericin B (L-AmB):

• Standard infections: 3-5 mg/kg/day IV 4, 2, 5
• CNS involvement or severe infections: 5-10 mg/kg/day IV 4, 5
• Cryptococcal meningitis: 4-6 mg/kg/day 5

Amphotericin B Lipid Complex (ABLC):

• 5 mg/kg/day IV 4, 2

Amphotericin B Colloidal Dispersion (ABCD):

• 3-6 mg/kg/day IV (maximum 3-4 mg/kg/day due to infusion-related toxicity) 4, 2

Administration Guidelines

Infusion Parameters

• Infuse over 2-6 hours depending on dose 1
• Use concentration of 0.1 mg/mL 2, 1
• May use in-line membrane filter with mean pore diameter ≥1.0 micron 1

Pre-medication to Reduce Toxicity

• Hydration: Administer 1 L of 0.9% normal saline 30 minutes before infusion to reduce nephrotoxicity 2, 5, 3
• Premedication: Give diphenhydramine or acetaminophen before infusion to reduce infusion-related reactions 2, 5, 3

Monitoring During Therapy

• Monitor renal function, electrolytes, and liver function tests regularly 2, 3
• Watch for infusion-related reactions: fever, chills, nausea, vomiting, chest pain, dyspnea, hypoxia 5, 3
• If severe reactions occur, temporarily interrupt infusion and administer IV diphenhydramine 5

Duration of Therapy by Indication

Candidemia (non-neutropenic):

• Continue for 14 days after last positive blood culture and resolution of signs/symptoms 4, 2, 3

Candidemia (neutropenic):

• Continue for 14 days after last positive blood culture 4

Chronic disseminated candidiasis:

• 3-6 months and until resolution or calcification of radiologic lesions 4, 2

Cryptococcal meningitis:

• At least 2 weeks of amphotericin B, followed by fluconazole 2, 3

Invasive aspergillosis:

• Up to 11 months with total dose up to 3.6 g 1

Mucormycosis:

• Cumulative dose of at least 3 g (minimum 3-4 g for deep tissue invasion) 1

Sporotrichosis:

• Up to 9 months with total dose up to 2.5 g 1

Special Populations

Pediatric patients:

• Conventional amphotericin B: 0.5-1.5 mg/kg/day IV 2, 3
• Alternative: 50 mg/m²/day 3

Neonates:

• 0.6-1.0 mg/kg/day IV for candidemia 4, 3
• For disseminated candidiasis: 1 mg/kg/day 3
• Duration: 14-21 days after resolution of signs/symptoms and negative blood cultures 4

Neutropenic patients:

• Conventional amphotericin B: 0.7-1.0 mg/kg/day 4
• Liposomal amphotericin B: 3.0-6.0 mg/kg/day 4

Critical Safety Considerations

Nephrotoxicity Management

• Primary toxicity is nephrotoxicity from glomerular damage 3
• Hydration with 0.9% saline IV 30 minutes before infusion significantly reduces nephrotoxicity 2, 5, 3
• Lipid formulations have substantially less nephrotoxicity than conventional amphotericin B 2, 6, 7, 8
• Liposomal amphotericin B provides the greatest renal protection among all formulations 2, 7

Infusion-Related Reactions

• Conventional amphotericin B causes fever (44%), chills/rigors (54%), hypotension, hypertension, and hypoxia 8
• Liposomal amphotericin B significantly reduces these reactions: fever (17%), chills/rigors (18%) 8
• ABCD has equivalent or more frequent infusion-related reactions than conventional amphotericin B 7

Common Pitfalls to Avoid

• Never reconstitute with saline - causes immediate precipitation 1
• Never use bacteriostatic water - causes precipitation 1
• Always check dextrose pH - must be >4.2 to prevent precipitation 1
• Do not use filters <1.0 micron - will block the colloidal dispersion 1
• For persistent candidemia despite therapy, investigate for deep tissue focus of infection 2, 3