What is the recommended dosage and administration of lyophilised (freeze-dried) amphotericin B for treating serious fungal infections?

Lyophilised Amphotericin B Dosage and Administration for Serious Fungal Infections

The recommended dosage of lyophilised amphotericin B for serious fungal infections is 0.5-1.5 mg/kg administered once daily intravenously over 1-2 hours, with a concentration of 0.1 mg/mL. 1, 2

Conventional Amphotericin B (Deoxycholate) Administration

Initial Dosing

• A test dose (1 mg in 20 mL of 5% dextrose solution) administered over 20-30 minutes is recommended before starting therapy to assess tolerance 2
• For patients with good cardio-renal function and well-tolerated test dose, therapy typically starts with 0.25 mg/kg daily 2
• For severe, rapidly progressive fungal infections, therapy may begin with 0.3 mg/kg daily 2
• For patients with impaired cardio-renal function or severe reaction to the test dose, start with smaller doses (5-10 mg) 2

Dose Adjustment and Maintenance

• Depending on patient's cardio-renal status, doses may be gradually increased by 5-10 mg per day 2
• Final daily dosage typically ranges from 0.5-0.7 mg/kg 1
• For life-threatening infections or those caused by less susceptible species (e.g., C. glabrata, C. krusei), dosages up to 1 mg/kg daily should be considered 1
• CAUTION: Under no circumstances should a total daily dose of 1.5 mg/kg be exceeded as overdoses can result in potentially fatal cardiac or cardiopulmonary arrest 2

Preparation and Administration

• Reconstitute by adding 10 mL of Sterile Water for Injection to create a 5 mg/mL concentrate 2
• Further dilute to 0.1 mg/mL with 5% Dextrose Injection (pH above 4.2) 2
• Administer over 1-2 hours for standard doses, or 3-6 hours for higher doses (>1 mg/kg) or patients with azotemia or hyperkalemia 1
• Hydration with 0.9% saline intravenously 30 minutes before infusion can ameliorate nephrotoxicity 1

Lipid Formulations of Amphotericin B

For patients with renal impairment, previous nephrotoxicity, or intolerance to conventional amphotericin B:

Types and Dosing

• Amphotericin B lipid complex (ABLC): 5 mg/kg daily IV 1
• Liposomal amphotericin B (L-AmB): 3-5 mg/kg daily IV 1
• Amphotericin B colloidal dispersion (ABCD): 3-6 mg/kg daily IV 1

Important Considerations

• Lipid formulations have similar efficacy but less nephrotoxicity compared to conventional amphotericin B 1, 3
• The three lipid formulations have different pharmacological properties and should not be interchanged without careful consideration 1
• Liposomal amphotericin B appears to provide the greatest renal protection among lipid formulations 1
• Infusion-related reactions (fever, chills, nausea) can occur but are generally less severe than with conventional formulation 1

Special Populations

Pediatric Patients

• For children with invasive candidiasis: 0.5-1.5 mg/kg daily IV of conventional amphotericin B 1
• For neonates: Similar kinetics as adults, 0.6-1.0 mg/kg daily IV 1
• Lipid formulations in children: Similar dosing as adults (ABLC: 5 mg/kg/day; L-AmB: 3-5 mg/kg/day) 1

Immunocompromised Patients

• For HIV-infected patients or immunosuppressed patients with severe fungal infections: Lipid formulations at 3-5 mg/kg daily are preferred 1
• For meningeal infections: Lipid formulation at 5 mg/kg daily for 4-6 weeks, followed by oral azole therapy 1

Duration of Therapy

• For candidemia: Continue treatment for 14 days after last positive blood culture and resolution of signs and symptoms 1
• For disseminated candidiasis: 3-6 months and until resolution or calcification of radiologic lesions 1
• For cryptococcal meningitis: At least 2 weeks of amphotericin B followed by fluconazole 1
• For aspergillosis: Treatment may extend up to 11 months with a total dose up to 3.6 g 2
• For sporotrichosis: Treatment may extend up to 9 months with a total dose up to 2.5 g 2

Monitoring and Adverse Effects

• Monitor renal function, electrolytes (particularly potassium), and liver function tests regularly 1, 4
• Nephrotoxicity typically develops within the first 9 days of treatment 4
• Infusion-related reactions (fever, chills, nausea, vomiting) can be ameliorated by premedication with diphenhydramine 1
• For patients with persistent candidemia despite appropriate therapy, investigate for deep tissue focus of infection (e.g., echocardiogram, renal or abdominal ultrasound) 1

Common Pitfalls and Caveats

• Never exceed the maximum recommended dose of 1.5 mg/kg/day to avoid potentially fatal cardiac complications 2
• The three lipid formulations are not interchangeable and have different dosing recommendations 1
• Central venous catheters should be removed when feasible in patients with fungemia 1
• Renal function should be closely monitored, particularly in patients receiving other nephrotoxic medications 1, 4
• Low-dose liposomal amphotericin B (1 mg/kg/day) may be considered for certain indications to reduce cost and toxicity while maintaining efficacy 5