Page 21 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 8 of 16 Guideline

Maintenance phase (secondary prophylaxis) If there is renal impairment at baseline with a creatinine
The panel recommends fluconazole 200 mg daily for at least clearance of < 30 mL/min or a deterioration in renal function,
10 more months (i.e. to complete a total of 12 months of the recommended induction regimens are the following:
antifungal treatment). Maintenance fluconazole should only • If liposomal amphotericin B is available, 1 week of
be stopped when the CD4 count is documented to be liposomal amphotericin B (3 mg/kg/day – 4 mg/kg/day)
> 200 cells/µL (on one occasion is sufficient) and the most and flucytosine, followed by 1 week of fluconazole (both
recent HIV viral load is suppressed. fluconazole and flucytosine dose adjusted according to
creatinine clearance).
Adolescents and children • Two weeks of fluconazole (dose adjusted according to
During the induction phase, amphotericin B should be creatinine clearance) and flucytosine (dose adjusted
prescribed at a daily dose of 1 mg/kg/day and flucytosine as according to creatinine clearance).
a (divided) daily dose of 100 mg/kg/day (Table 5). • If neither flucytosine nor liposomal amphotericin B is
Fluconazole doses should also be calculated by body weight: available, administer a single dose of amphotericin B
induction phase: 12 mg/kg/day (up to 800 mg daily); deoxycholate (0.7 mg/kg) and daily fluconazole (dose
consolidation phase: 6 mg/kg/day – 12 mg/kg/day (up to adjusted according to creatinine clearance) and monitor
800 mg daily); and maintenance phase: 6 mg/kg/day (up to creatinine clearance daily. Administer amphotericin B
200 mg daily). deoxycholate (0.7 mg/kg) on alternate days if the
creatinine clearance remains static and give as many
Renal impairment (creatinine clearance < 50 mL/min) doses as possible over the 2-week induction period.
If there is renal impairment at the time of diagnosis of CM Important practice point
with a calculated creatinine clearance of 30 mL/min – 50 mL/
min, the recommended induction regimens are the following: Clinicians should be very clear when prescribing liposomal
amphotericin B versus amphotericin B deoxycholate. The
• If liposomal amphotericin B is available, switch to 1 week daily doses are different.
of liposomal amphotericin B (3 mg/kg/day – 4 mg/kg/
day) and flucytosine, followed by 1 week of fluconazole Intravenous fluids should be administered to all patients.
(both fluconazole and flucytosine dose adjusted according Tenofovir and amphotericin B deoxycholate can be used
to creatinine clearance) (Table 6). together provided the patient’s renal function is normal and
• One week of amphotericin B deoxycholate (1 mg/kg/day) serum creatinine does not double on treatment. Among
and flucytosine (dose adjusted according to creatinine patients with renal impairment, ART regimens containing
clearance), followed by 1 week of fluconazole (dose tenofovir should be adjusted, switching to an alternative
adjusted according to creatinine clearance) (Table 6). antiretroviral agent such as abacavir. If the patient’s initial

TABLE 5: Flucytosine dosing in children and adults with normal renal function.
Lower weight Upper weight Number of Total dose Daily dose for lower Daily dose for upper Dose 1† Dose 2† Dose 3† Dose 4†
limit (kg) limit (kg) pills (mg) weight limit (mg/kg) weight limit (mg/kg)
20 24 4 2000 100.00 83.33 1 1 1 1
25 29 5 2500 100.00 86.21 2 1 1 1
30 34 6 3000 100.00 88.24 2 1 2 1
35 39 7 3500 100.00 89.74 2 2 2 1
40 44 8 4000 100.00 90.91 2 2 2 2
45 49 9 4500 100.00 91.84 3 2 2 2
50 54 10 5000 100.00 92.59 3 2 3 2
55 59 11 5500 100.00 93.22 3 3 3 2
60 64 12 6000 100.00 93.75 3 3 3 3
65 69 13 6500 100.00 94.20 4 3 3 3
70 74 14 7000 100.00 94.59 4 3 4 3
75 79 15 7500 100.00 94.94 4 4 4 3
80 84 16 8000 100.00 95.24 4 4 4 4
†, Number of 500 mg pills per dose.
TABLE 6: Induction therapy doses of flucytosine, fluconazole and amphotericin B adjusted according to estimated glomerular filtration rates for adults.
Antifungal agent eGFR > 50 eGFR 10–50 eGFR < 10 Haemodialysis
Amphotericin B deoxycholate 1 mg/kg 1 mg/kg 1 mg/kg 1 mg/kg (can administer during dialysis)
Fluconazole 1200 mg daily 600 mg daily 600 mg daily 600 mg daily; dose after dialysis
Flucytosine 25 mg/kg 6 hourly 25 mg/kg 12 hourly 25 mg/kg daily 25 mg/kg daily; dose after dialysis
Source: The Sanford guide to antimicrobial therapy 2019 / editors, David N. Gilbert, M.D., George M. Eliopoulos, M.D., Henry F. Chambers, M.D., Michael S. Saag, M.D., Andrew T. Pavia, M.D.
Sperryville, VA, USA: Antimicrobial Therapy, Inc., [2019]
Note: Multiply by 0.85 for women. Children: CrCL 20 mL/min – 40 mL/min: flucytosine 25 mg/kg q12h; 10 mL/min – 20 mL/min: flucytosine 25 mg/kg q24 h; < 10 mL/min: flucytosine 25 mg/kg
q24–48h. Glomerular filtration rate (GFR) is a key indicator of renal function. Estimated GFR (eGFR) is a mathematically derived entity based on a patient’s serum creatinine level, age, sex and race.
Creatinine clearance (CrCL), an estimate of GFR, can be estimated in adults using the Cockcroft–Gault equation: [[140-age (years)]*weight (kg)] / [0.8136*serum creatinine (µmol/L)].

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