What is the recommended dosage of intravenous (IV) amphotericin B (antifungal medication)?

Amphotericin B Dosage

For invasive fungal infections, conventional amphotericin B deoxycholate should be dosed at 0.5-1.5 mg/kg IV daily, with lipid formulations (liposomal amphotericin B) at 3-5 mg/kg IV daily, administered over 2-6 hours depending on dose and patient tolerance. 1, 2, 3

Conventional Amphotericin B Deoxycholate Dosing

Standard Dosing

• Administer 0.5-0.7 mg/kg IV daily for most invasive candidal infections 1
• For severe or life-threatening infections, use 0.7-1.0 mg/kg IV daily 1, 2
• For less susceptible species (C. glabrata, C. krusei), increase to 1.0 mg/kg IV daily 1
• Maximum daily dose should never exceed 1.5 mg/kg 1, 3

Initiation Strategy

• For mild-to-moderate disease, start at 0.25-0.5 mg/kg and increase as tolerated to target dose 1
• For life-threatening disease, administer the full target dose from day one 1
• The manufacturer's 1 mg test dose over 20-30 minutes is optional but may delay therapeutic dosing 3, 4

Infusion Parameters

• Infuse over 2-6 hours at a concentration of 0.1 mg/mL (1 mg/10 mL) in 5% dextrose 1, 3
• For patients with azotemia, hyperkalemia, or receiving high doses (>1 mg/kg), extend infusion to 3-6 hours 1
• Infusion rate should not exceed 50 mg/hour in patients with adequate renal function 4

Lipid Formulations

Liposomal Amphotericin B (L-AmB)

• Standard dose: 3-5 mg/kg IV daily for most invasive fungal infections 1, 2, 5
• For CNS involvement (including cryptococcal meningitis): 5-10 mg/kg IV daily 1, 5
• For mucormycosis: 5-10 mg/kg IV daily, with full dose from day one 1
• Liposomal amphotericin B provides the greatest renal protection among all formulations 1, 5, 6

Amphotericin B Lipid Complex (ABLC)

• Dose: 5 mg/kg IV daily 1, 7
• Appropriate for patients without CNS involvement 1

Amphotericin B Colloidal Dispersion (ABCD)

• Dose: 3-4 mg/kg IV daily (maximum) 1, 7, 8
• This formulation has dose-limiting infusion-related toxicity and is no longer commercially available in many regions 8

Nephrotoxicity Prevention

Mandatory Hydration Protocol

• Administer 1 liter of 0.9% normal saline IV over 30 minutes before each amphotericin B infusion 1, 2, 7, 5
• This intervention significantly reduces nephrotoxicity and should never be skipped in patients who can tolerate fluids 7, 5
• For patients who develop substantial azotemia, reduce dose or switch to lipid formulation 1

Infection-Specific Dosing

Candidemia and Invasive Candidiasis

• Conventional amphotericin B: 0.5-1.5 mg/kg IV daily 1, 2
• Continue for 2-3 weeks after last positive blood culture and resolution of symptoms 1, 2
• Remove central venous catheters when feasible 1

CNS Candidiasis

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

Cryptococcal Meningitis

• Liposomal amphotericin B: 4-6 mg/kg IV daily for at least 2 weeks 2, 7
• For children: 2 mg/kg IV daily, up to 7.5 mg/kg daily for refractory cases 7

Invasive Aspergillosis

• Conventional amphotericin B: 1.0-1.5 mg/kg IV daily 1
• Liposomal amphotericin B: 3-5 mg/kg IV daily 1
• Treatment duration up to 11 months with total dose up to 3.6 g has been used 3

Mucormycosis

• Liposomal amphotericin B: 5-10 mg/kg IV daily from day one 1
• Amphotericin B lipid complex: 5 mg/kg IV daily for non-CNS involvement 1
• Do not slowly escalate doses; give full therapeutic dose immediately 1

Histoplasmosis

• For moderately severe to severe disease: Lipid formulation 3.0-5.0 mg/kg IV daily for 1-2 weeks 1
• Conventional amphotericin B: 0.7-1.0 mg/kg IV daily is an alternative in patients at low risk for nephrotoxicity 1

Sporotrichosis

• Total dose up to 2.5 g over up to 9 months of therapy 3

Rhinocerebral Phycomycosis

• Cumulative dose of at least 3 g is recommended 3
• Total dose of 3-4 g is a reasonable minimum where there is clinical evidence of deep tissue invasion 3

Pediatric Dosing

Neonates and Infants

• For disseminated candidiasis: 1 mg/kg IV daily 1, 2
• Liposomal amphotericin B: Not approved in infants <1 month of age; 3 mg/kg IV daily for older infants 1

Children

• Conventional amphotericin B: 0.5-1.5 mg/kg IV daily or 50 mg/m²/day 1, 2
• For children 2-12 years or 12-14 years weighing <50 kg: Adjust echinocandin doses accordingly, but amphotericin B dosing remains weight-based 1

Alternate Day Dosing

• After stabilization and resolution of fever, amphotericin B can be given as 1.5 mg/kg IV every other day 1

Infusion-Related Reaction Management

Premedication

• Administer diphenhydramine or acetaminophen before infusion to reduce reactions 7, 5
• Use prophylactically in patients with history of hypersensitivity reactions 4

Monitoring During Infusion

• Monitor temperature, pulse, respiration, and blood pressure every 30 minutes for 2-4 hours after test dose 3
• Watch for fever, chills, nausea, vomiting, chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, and urticaria 7, 5
• If severe reactions occur, temporarily interrupt infusion and administer IV diphenhydramine 7

Special Administration Routes

Intrathecal/Intraventricular

• Dose: 0.1-1.5 mg per dose for intrathecal administration 1
• For intraventricular via CNS devices: 0.01-0.5 mg in 2 mL of 5% dextrose in water 7, 5

Intravitreal Injection

• Dose: 5-10 μg/0.1 mL sterile water 7, 5

Bladder Irrigation

• Dose: 50 mg/L sterile water daily for 5 days for fungal cystitis 7, 4

Monitoring Requirements

• Monitor renal function, electrolytes (especially potassium), and liver function tests regularly throughout therapy 1, 2, 7, 5
• For persistent fungemia despite appropriate therapy, investigate for deep tissue focus with echocardiogram, renal, or abdominal ultrasound 1, 2

Critical Warnings

• Permanent nephrotoxicity is related to cumulative dose 1
• Amphotericin B overdoses can result in potentially fatal cardiac or cardiopulmonary arrest 3
• Lipid formulations should be used preferentially in patients with renal impairment 7, 5, 6
• The three lipid formulations have different pharmacological properties and should not be interchanged without careful consideration 1