Timing of Liposomal Amphotericin B Dose Escalation
Wait until 1300 to give the 5 mg/kg dose, maintaining the established 24-hour dosing interval from the previous 3 mg/kg dose. Liposomal amphotericin B is administered once daily, and the dosing schedule should be consistent to maintain appropriate pharmacokinetic parameters and minimize toxicity 1, 2.
Rationale for Maintaining 24-Hour Intervals
Once-daily dosing of liposomal amphotericin B is standard across all formulations and indications. The lipid formulations are designed for administration every 24 hours, regardless of the specific dose being given 1, 3, 2. This applies whether you're using 3 mg/kg, 5 mg/kg, or even 10 mg/kg for CNS involvement 4, 1, 2.
- Pharmacokinetic studies demonstrate that liposomal amphotericin B maintains therapeutic levels above minimum inhibitory concentrations for common fungi when dosed once daily 5
- The small size and negative charge of liposomal amphotericin B allows it to avoid rapid uptake by the mononuclear phagocyte system, resulting in higher peak plasma levels and a larger area under the concentration-time curve compared to conventional formulations 6
- Administering the dose early (at 0100, only 12 hours after the previous dose) would result in drug accumulation and potentially increase toxicity without improving efficacy 7, 6
Dose Escalation Context
When escalating from 3 mg/kg to 5 mg/kg, the timing should remain consistent with the established schedule. The dose increase itself is appropriate for several clinical scenarios:
- Standard treatment for severe fungal infections without CNS involvement uses 3-5 mg/kg/day 4, 1, 2
- For COVID-19 associated mucormycosis, 5 mg/kg/day is the recommended dose for patients without CNS involvement 4, 2
- For sporotrichosis and other disseminated fungal infections, 3-5 mg/kg/day is standard 4
Common Pitfall to Avoid
Do not confuse dose escalation with the need for more frequent dosing. The increase from 3 mg/kg to 5 mg/kg represents an intensification of therapy, not a change in dosing frequency 1, 2. Liposomal amphotericin B remains a once-daily medication regardless of the dose used 4, 1, 3, 2.
- Even at the highest recommended dose of 10 mg/kg/day for CNS infections, the medication is still given once daily 4, 1, 2
- Giving doses more frequently than every 24 hours is not supported by any guideline or pharmacokinetic data 1, 3, 2
Practical Administration Recommendation
Administer the 5 mg/kg dose at 1300 today (24 hours after the previous 3 mg/kg dose), then continue daily dosing at 1300 going forward. This maintains therapeutic drug levels while minimizing the risk of nephrotoxicity and other adverse effects 4, 1, 2.
- Pre-medicate with diphenhydramine or acetaminophen 30 minutes before infusion to reduce infusion-related reactions 4, 1, 2
- Administer 1 L of normal saline before and after the infusion if the patient can tolerate fluids to reduce nephrotoxicity 4, 1
- Monitor for infusion-related reactions including fever, chills, chest pain, dyspnea, and hypoxia 1