What is the recommended administration protocol for amphotericin B (antifungal medication) liposomal?

Administration of Liposomal Amphotericin B

Liposomal amphotericin B should be reconstituted with sterile water for injection, diluted in 5% dextrose solution, and administered intravenously over 1-2 hours at a concentration of 0.2-0.5 mg/mL. 1

Preparation Steps

• Reconstitute the product with sterile water for injection (NOT bacteriostatic water containing preservatives)
• Shake vigorously for at least 30 seconds until all material is completely dispersed
• The reconstituted solution should have a concentration of approximately 4 mg/mL
• Filter through the provided 5-micron filter
• Dilute with 5% dextrose solution to achieve a final concentration of 0.2-0.5 mg/mL
• Do NOT mix with saline solutions, other drugs, or electrolytes 1
• Do NOT filter through membrane filters less than 1 micron 1

Dosage Recommendations

Dosage varies by indication:

• Invasive candidiasis: 3-5 mg/kg once daily 1
• Cryptococcal meningitis in HIV patients: 3-4 mg/kg once daily 1
• Invasive aspergillosis: 3-5 mg/kg daily 2, 3
• Fluconazole/voriconazole-resistant isolates: 3-5 mg/kg intravenous daily 2
• Mucormycosis: 5-10 mg/kg daily (with 10 mg/kg recommended for CNS involvement) 2

Important Dosing Considerations

• For initial treatment of CNS fungal infections, 5 mg/kg daily is recommended 2
• Higher doses (10 mg/kg) do not show additional benefit for invasive aspergillosis but increase nephrotoxicity 3
• Full daily dose should be given from the first treatment day rather than slowly increasing over several days 2

Administration Protocol

1. Pre-medication: Administer diphenhydramine or acetaminophen before infusion to reduce infusion-related reactions 2, 1
2. Hydration: For patients who can tolerate fluids, administer 1L of normal saline before and after infusion to reduce nephrotoxicity 2
3. Infusion rate: Administer over 1-2 hours; do not administer too rapidly as this increases risk of infusion reactions 1
4. For CNS infections: Infuse at a rate of 0.08 mg/kg/hour over 6-8 hours 2

Monitoring During Administration

• Monitor vital signs before, during, and after infusion until stable

• Watch for infusion-related reactions (occur in ~20% of patients, with 85% occurring within first 5 minutes):

  • Chest pain
  • Dyspnea
  • Hypoxia
  • Abdominal/flank pain
  • Flushing
  • Urticaria 1

• If reactions occur:

  • Temporarily interrupt infusion
  • Administer diphenhydramine
  • Resume at a slower rate once symptoms resolve 1

Ongoing Monitoring

• Baseline and frequent (1-2 times weekly) monitoring of:
  • Serum chemistry values
  • Complete blood count
  • Renal function
  • Electrolytes, particularly potassium and magnesium 1

Pitfalls and Caveats

1. Do not confuse different amphotericin B formulations: Liposomal amphotericin B (AmBisome) is distinct from amphotericin B lipid complex (ABLC/Abelcet) and amphotericin B colloidal dispersion (ABCD). These formulations have different pharmacological properties and should not be interchanged 2

2. Nephrotoxicity management: Nephrotoxicity is less common with liposomal formulation compared to conventional amphotericin B deoxycholate but still occurs. Pre- and post-infusion hydration with normal saline can reduce this risk 2, 4

3. Solution incompatibilities: Never mix with saline solutions, as this can cause precipitation. Only use 5% dextrose as the diluent 1

4. Duration of therapy: Treatment should continue for at least 4-6 weeks for most invasive fungal infections, with final duration depending on resolution of lesions as determined by repeated examinations 2

By following these administration guidelines, you can optimize the efficacy of liposomal amphotericin B while minimizing the risk of adverse effects.