TABLE 7.

Summary of recommendation 4.

Scenario	Sub-recommendations
Administration of amphotericin B deoxycholate†	Amphotericin B powder should be reconstituted in sterile water; inject the calculated volume of reconstituted antifungal in water into 1 L of 5% dextrose water and administer within 24 h Amphotericin B can be administered via a peripheral intravenous (IV) line if the solution contains ≤ 0.1 mg of amphotericin B per 1 mL of 5% dextrose water A test dose is unnecessary The solution should be infused over at least 4 h
Administration of flucytosine	Flucytosine is available as 500 mg tablets With normal renal function, the dose is 100 mg/kg/day per os in four divided doses Therapeutic monitoring of serum levels is not recommended at this dose
Prevention of amphotericin B deoxycholate-related toxicities	Adults should be pre-hydrated with 1 L of normal saline containing 1 ampoule of potassium chloride (20 mmol) infused over 2 h before the amphotericin B infusion‡ Twice daily oral potassium and daily oral magnesium supplementation should be administered to adults To minimise the risk of phlebitis, lines should be flushed with normal saline immediately after the amphotericin B infusion is complete and the infusion bag should not be left attached to the intravenous administration set after the infusion is complete
Prevention of flucytosine-related toxicity	Drug accumulation and increased risk for toxicity occurs with renal dysfunction. The dose therefore needs to be carefully adjusted according to the estimated glomerular filtration rate
Monitoring of patients receiving amphotericin B and flucytosine	Days 0, 3 and 7: creatinine and potassium (and magnesium, if available) Days 0 and 7: full blood count (with a differential count if available). Day 3: full blood count and differential can be considered when flucytosine is used, especially if baseline abnormalities exist. Flucytosine may cause bone marrow suppression but this is uncommonly observed with short duration of use and the current suggested dosing schedule Fluid input and output monitoring
Management of amphotericin B-related toxicities	Refer to Recommendation 3 (baseline renal impairment section) Febrile reactions can be treated with paracetamol 1 g 30 min before infusion (if severe, hydrocortisone 25 mg IV can be given before subsequent infusions)
Management of flucytosine-related toxicities	If grade 4 neutropenia or if any neutropenia-related complications develop, reduce the flucytosine dose and repeat a neutrophil count immediately. If neutropenia is confirmed, stop the flucytosine and switch to fluconazole. If the patient was being treated with amphotericin B and flucytosine, consider a second week of amphotericin B deoxycholate treatment.

^†, For adolescents and children, doses should be calculated by body weight;

^‡, For children and adolescents, normal saline, with 1 ampoule of potassium chloride (20 mmol) added per litre of fluid, should be infused at 10 mL/kg – 15 mL/kg over 2–4 h (not more than 1 L) prior to amphotericin B administration. If saline is unavailable, then other parenteral rehydration solutions, for example, Darrow’s solution or Ringer’s lactate, that already contain potassium can be used.