Page 24 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 11 of 16 Guideline

The dose of flucytosine should be adjusted according to the blood count should be done at least weekly. A baseline
estimated creatinine clearance in order to prevent differential count should be done if available and be
accumulation and increased toxicity (Table 6). repeated with subsequent full blood counts. Creatinine
clearance needs to be monitored in order to adjust flucytosine
Laboratory or clinical monitoring dose. This is particularly important where baseline renal
function impairment exists or where flucytosine is
Recommendations depend on the induction regimen administered with amphotericin B deoxycholate (Table 6).
(Table 8).

Fluconazole
Amphotericin B deoxycholate
The panel recommends checking alanine transaminase (ALT)
At a minimum, baseline and twice weekly monitoring of levels if symptoms of hepatitis or jaundice develop while
serum creatinine/potassium and baseline and weekly patients are on fluconazole, but routine ALT monitoring is
monitoring of haemoglobin are recommended for the not indicated.
duration of amphotericin B deoxycholate treatment. Renal
toxicity is more likely to develop in the second week of
treatment in regimens where amphotericin B is used for 2 Management of toxicities
weeks. Fluid input and output should be carefully monitored. Amphotericin B deoxycholate
Chemical phlebitis is often complicated by infection at the For significant hypokalaemia (serum K <3.3 mmol/L),
+
intravenous line insertion site, which can result in additional intravenous replacement is required: up to 2
bacteraemia ; the insertion site should be monitored by ampoules of potassium chloride (20 mmol K+ per 10 mL
56
regular clinical examination and febrile patients with a ampoule) in 1 L of normal saline 8 hourly. Among those
suspected insertion site infection should be appropriately who develop hypokalaemia, serum potassium should be
investigated and managed. monitored daily until it is resolved. If hypokalaemia
remains uncorrected, serum magnesium should be checked
Flucytosine (if this test is available) and/or oral magnesium
Baseline grade 1 neutropenia (defined as an absolute supplementation should be doubled. Intravenous
neutrophil count ≤ 1000 cells/mm ) was documented among magnesium sulphate may be considered for persistent
3
12% of participants enrolled into the Cryptococcal Optimal hypokalaemia and hypomagnesaemia. If serum creatinine
ART Timing and Adjunctive Sertraline for the Treatment of doubles from baseline, one dose of amphotericin B
HIV-Associated Cryptococcal Meningitis clinical trials where deoxycholate may be omitted and/or pre-hydration may be
they received amphotericin B and fluconazole (plus sertraline increased to 1 L of normal saline 8 hourly; serum creatinine
57
in some patients). Patients with baseline grade 1 should then be monitored daily. If serum creatinine
neutropenia did not have a higher 30-day mortality improves, amphotericin B may be restarted at a dose of
compared to those without neutropenia. A baseline full 0.7 mg/kg/day and/or alternate-day treatment could be
blood/differential count should be done where available considered. If creatinine remains elevated or repeatedly
and the risk–benefit ratio of flucytosine therapy should be rises, liposomal amphotericin B should be substituted if
considered in the setting of baseline neutropenia. However, available or amphotericin B deoxycholate should be
we strongly recommend the use of flucytosine even when stopped and an alternative regimen should be used (refer
there is baseline neutropenia because of the substantial to Recommendation 3). If febrile reactions occur with
mortality benefit over alternative regimens. Both amphotericin B, paracetamol 1 g may be given 30 min before
amphotericin B and flucytosine are associated with anaemia infusion or, for severe reactions, hydrocortisone 25 mg IV
and thus serum haemoglobin should be monitored. A full can be administered before subsequent infusions. 22
TABLE 8: Laboratory monitoring according to induction regimen used.
Induction regimen Week 1 Week 2 Laboratory monitoring
Preferred Amphotericin B Fluconazole Day 0: Full blood count and differential, creatinine clearance, potassium, magnesium
deoxycholate + 5-FC Day 3: Full blood count (only if low baseline haemoglobin), creatinine clearance, potassium, magnesium
Day 7: Full blood count and differential, creatinine clearance, potassium, magnesium
Amphotericin B Fluconazole + 5-FC Fluconazole + 5-FC Day 0: Full blood count and differential, creatinine clearance
unavailable
Day 3: Full blood count (if low baseline haemoglobin)
Day 7: Full blood count and differential
Day 10: Full blood count and differential (if any abnormalities previously)
Day 14: Full blood count and differential, creatinine clearance can be done more frequently if baseline is
abnormal
5-FC is unavailable Amphotericin B Amphotericin B Day 0: Creatinine clearance, potassium, magnesium, full blood count
deoxycholate + deoxycholate +
fluconazole fluconazole Day 3: Creatinine clearance, potassium, magnesium
Day 7: Creatinine clearance, potassium, magnesium, full blood count
Day 10: Creatinine clearance, potassium, magnesium
Day 14: Creatinine clearance, potassium, magnesium, full blood count

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