What is the recommended dose of Amphotericin B (antifungal medication) for treating fungal infections?

Amphotericin B Dosing for Fungal Infections

For conventional amphotericin B deoxycholate, administer 0.5-1.0 mg/kg/day IV for most invasive fungal infections, while lipid formulations should be dosed at 3-5 mg/kg/day IV, with the specific formulation and dose selected based on infection severity, renal function, and the specific fungal pathogen. 1, 2

Conventional Amphotericin B Deoxycholate Dosing

Standard dosing is 0.6-1.0 mg/kg/day IV, with the maximum daily dose never exceeding 1.5 mg/kg due to risk of fatal cardiac arrest. 1, 3

• For severe or life-threatening infections, use 0.7-1.0 mg/kg/day 2, 4
• For less severe infections or patients with impaired cardio-renal function, start with 0.25-0.3 mg/kg/day and gradually increase by 5-10 mg increments 3
• Infuse over 2-6 hours at a concentration of 0.1 mg/mL (1 mg/10 mL) in 5% dextrose 3
• Administer 1 liter of 0.9% normal saline 30 minutes before infusion to reduce nephrotoxicity 2, 4

Test Dose Considerations

The FDA label recommends a 1 mg test dose in 20 mL of 5% dextrose infused over 20-30 minutes, with vital signs monitored every 30 minutes for 2-4 hours 3. However, this practice may delay therapeutic dosing without clear benefit in most patients.

Lipid Formulations of Amphotericin B

Lipid formulations provide equivalent efficacy with significantly reduced nephrotoxicity compared to conventional amphotericin B, making them preferred for patients with renal impairment or those at high risk for nephrotoxicity. 1, 5, 6

Specific Lipid Formulation Dosing

• Liposomal amphotericin B (AmBisome): 3-5 mg/kg/day IV 2, 7, 4

  • For CNS infections: 5-10 mg/kg/day 4
  • Provides the greatest renal protection among all formulations 2, 4
  • Significantly fewer infusion-related reactions than conventional amphotericin B 8

• Amphotericin B lipid complex (ABLC/Abelcet): 5 mg/kg/day IV 2, 7

  • Achieves higher lung tissue concentrations than other formulations 6
  • Approved only for second-line therapy in patients intolerant of or refractory to conventional amphotericin B 1

• Amphotericin B colloidal dispersion (ABCD): 3-6 mg/kg/day IV 2

  • Associated with dose-limiting infusion-related reactions; do not exceed 4 mg/kg/day 6
  • No longer commercially available in many markets 6

Infection-Specific Dosing

Candidemia and Invasive Candidiasis

• Conventional amphotericin B: 0.6-1.0 mg/kg/day IV 1
• Lipid formulations: 3-5 mg/kg/day IV 1
• Continue treatment for 14 days after the last positive blood culture and resolution of signs/symptoms 2, 7

CNS Candidiasis

• Liposomal amphotericin B 5 mg/kg/day IV, with or without flucytosine 25 mg/kg four times daily 4

Coccidioidomycosis with Meningitis

• Intrathecal amphotericin B: 0.1-1.5 mg per dose, starting at low doses and increasing until patient intolerance 1
• Administered at intervals ranging from daily to weekly 1

Sporotrichosis

• Conventional amphotericin B up to a total cumulative dose of 2.5 grams over up to 9 months 3

Aspergillosis

• Conventional amphotericin B up to a total cumulative dose of 3.6 grams over up to 11 months 3

Rhinocerebral Phycomycosis

• A minimum cumulative dose of 3-4 grams is recommended for deep tissue invasion 3
• This aggressive dosing is necessary given the rapidly fatal course of this infection 3

Special Populations

Pediatric Patients

• For invasive candidiasis: 0.5-1.5 mg/kg/day IV or 50 mg/m²/day 7
• For neonates with disseminated candidiasis: 1 mg/kg/day IV 7
• For neonatal disseminated cutaneous candidiasis in premature/low birth weight infants: 0.5-1 mg/kg/day for a total dose of 10-25 mg/kg 1, 4

Pregnancy

• Amphotericin B is the preferred antifungal during pregnancy, with lipid formulations at 3-5 mg/kg/day recommended for severe infections 7

Renal Impairment

• Lipid formulations are strongly preferred over conventional amphotericin B in patients with baseline renal dysfunction 4
• If conventional amphotericin B must be used, start with lower doses (5-10 mg/day) and increase gradually 3

Critical Administration Guidelines

Preparation

• Reconstitute with sterile water for injection (without bacteriostatic agents) to create 5 mg/mL concentrate 3
• Dilute 1:50 with 5% dextrose injection (pH >4.2) to achieve final concentration of 0.1 mg/mL 3
• Never use saline solutions or diluents containing bacteriostatic agents, as these cause precipitation 3
• Use aseptic technique throughout; no preservatives are present 3

Infusion Parameters

• Infuse over 2-6 hours depending on dose 3
• May use in-line membrane filter with mean pore diameter ≥1 micron 3
• Pre-hydrate with 1 liter 0.9% normal saline 30 minutes before infusion in patients who can tolerate fluids 2, 4

Premedication for Infusion Reactions

• Acetaminophen or diphenhydramine can be used prophylactically in patients with history of reactions 7
• Administer as needed for fever, chills, nausea, or vomiting 7

Monitoring Requirements

Monitor renal function, electrolytes (particularly potassium and magnesium), and liver function tests regularly throughout therapy. 2, 7, 4

• Watch for infusion-related reactions: fever, chills, nausea, vomiting, chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, urticaria 4
• Nephrotoxicity is defined as substantial azotemia from glomerular damage 7
• For persistent candidemia despite appropriate therapy, investigate for deep tissue foci of infection 2, 7

Critical Pitfalls to Avoid

• Never exceed 1.5 mg/kg/day total dose of conventional amphotericin B due to risk of fatal cardiac arrest 3
• Do not skip pre-hydration with normal saline, as this significantly increases nephrotoxicity risk 4
• Do not interchange different lipid formulations without careful consideration, as they have different pharmacological properties and toxicity profiles 1
• Do not use conventional amphotericin B when lipid formulations are available for patients with renal impairment 4
• Avoid delaying therapeutic dosing with prolonged test dose protocols in critically ill patients 3