Should I give an extra spot dose of amphotericin B at 0100 to compensate for the lower 3 mg/kg infusion, or maintain the 24‑hour interval and administer the next 5 mg/kg dose at the scheduled 1300 time?

No Spot Dose at 0100 – Maintain the 24‑Hour Interval

Do not give an extra spot dose at 0100; instead, administer the next scheduled 5 mg/kg dose at 1300 (24 hours after the prior dose) to preserve the once‑daily dosing interval and minimize nephrotoxicity. 1

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Rationale for Once‑Daily Dosing

• All liposomal amphotericin B formulations—whether 3 mg/kg, 5 mg/kg, or up to 10 mg/kg for CNS involvement—are administered once daily. 1
• When escalating from 3 mg/kg to 5 mg/kg, the 24‑hour dosing interval must be preserved; the higher dose does not require more frequent administration. 1
• Even at the maximum recommended dose of 10 mg/kg per day for CNS infections, the medication is still given once daily. 1

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Why Not Give a "Make‑Up" Dose at 0100

• Administering an unscheduled dose at 0100 would create a shortened interval (e.g., 12 hours) followed by another dose at 1300, effectively doubling the daily exposure within 24 hours and increasing the risk of nephrotoxicity without improving efficacy. 1, 2
• Amphotericin B nephrotoxicity is dose‑dependent and cumulative; maintaining consistent 24‑hour intervals minimizes renal injury while preserving therapeutic drug levels. 2, 3, 4
• The pharmacokinetics of liposomal amphotericin B support once‑daily dosing: a single dose produces a high peak plasma level (Cmax) and a large area under the concentration‑time curve, with tissue concentrations highest in the liver and spleen and sustained over 24 hours. 2

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Correct Dosing Schedule Going Forward

• Administer the 5 mg/kg dose exactly 24 hours after the prior 3 mg/kg dose (at 1300) and continue daily dosing at the same clock time to maintain therapeutic drug levels while minimizing nephrotoxicity. 1
• Premedicate with diphenhydramine or acetaminophen 30 minutes before the infusion to reduce infusion‑related reactions. 1, 5
• Give 1 L of normal saline before and after the infusion, provided the patient can tolerate the fluid volume, to lessen the risk of nephrotoxicity. 1, 5

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Monitoring and Safety

• Monitor renal function, electrolytes, and liver function tests regularly during therapy. 1, 6
• Watch for infusion‑related reactions including fever, chills, nausea, and vomiting; temporarily interrupt the infusion and administer intravenous diphenhydramine if severe reactions occur. 1
• If nephrotoxicity develops (serum creatinine increase ≥ 0.5 mg/dL above baseline), consider switching to a lipid formulation if not already using one, or reducing the dose if clinically feasible. 7, 3

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Common Pitfall to Avoid

• Do not attempt to "catch up" on a lower dose by adding an extra infusion within the same 24‑hour period; this practice increases toxicity without enhancing efficacy and is not supported by any guideline or pharmacokinetic data. 1, 2