Page 22 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 9 of 16 Guideline

reason for a reduced creatinine clearance was dehydration Analgesia
and this has been corrected with fluid administration, the Therapeutic LPs are the best form of ‘analgesia’ for headaches
patient can be switched back to amphotericin B deoxycholate associated with raised intracranial pressure. Paracetamol can
at normal doses. Flucytosine has a short plasma half-life and be used but not non-steroidal anti-inflammatory drugs
is cleared unchanged via the kidneys. Flucytosine requires (NSAIDs) because of the nephrotoxicity concerns with
dose adjustment if there is renal impairment; where patients amphotericin B deoxycholate. Morphine may also be
are dialysed, it should be given after dialysis (Table 6). appropriate and is not contraindicated in the presence of
Fluconazole monotherapy is not recommended except as a raised intracranial pressure.
last resort. When used as monotherapy during induction, the
fluconazole dose is 1200 mg daily with normal renal function. Recommendation 4: Amphotericin B
With a creatinine clearance of < 50 mL/min, the induction
dose of fluconazole should be reduced by 50% to 600 mg and flucytosine toxicity prevention,
daily. monitoring and management

Management of other forms of disseminated TABLE 7: Summary of recommendation 4.
cryptococcosis
Scenario Sub-recommendations
Cryptococcal fungaemia (i.e. a positive blood culture) Administration of • Amphotericin B powder should be reconstituted
should be managed as per CM. The treatment of amphotericin B in sterile water; inject the calculated volume
of reconstituted antifungal in water into
deoxycholate†
cryptococcomas, pulmonary cryptococcosis and other 1 L of 5% dextrose water and administer
within 24 h
forms of culture-confirmed disseminated cryptococcal • Amphotericin B can be administered via a
disease is beyond the scope of this guideline. Readers are peripheral intravenous (IV) line if the solution
contains ≤ 0.1 mg of amphotericin B per 1 mL of
5% dextrose water
advised to consult the 2010 Infectious Diseases Society of • A test dose is unnecessary
America guideline. 25 • The solution should be infused over at least 4 h
Administration of • Flucytosine is available as 500 mg tablets
flucytosine • With normal renal function, the dose is 100 mg/
Patients on tuberculosis treatment kg/day per os in four divided doses
• Therapeutic monitoring of serum levels is not
The panel does not recommend a fluconazole dose increase recommended at this dose
among patients receiving rifampicin because the induction of Prevention of amphotericin • Adults should be pre-hydrated with 1 L of
fluconazole metabolism by rifampicin causes only moderate B deoxycholate-related normal saline containing 1 ampoule of
potassium chloride (20 mmol) infused
toxicities
reductions in fluconazole exposure and because of the high over 2 h before the amphotericin B
infusion‡
doses of fluconazole that are now being recommended for • Twice daily oral potassium and daily oral
magnesium supplementation should be
induction and consolidation treatment. 8,47 administered to adults
• To minimise the risk of phlebitis, lines should be
flushed with normal saline immediately after the
Adjunctive corticosteroid therapy amphotericin B infusion is complete and the
infusion bag should not be left attached to the
The expert panel advises against adjunctive corticosteroid intravenous administration set after the infusion
is complete
therapy in the initial management of CM. Refer to Prevention of flucytosine- • Drug accumulation and increased risk for
9
Recommendation 7 for the use of corticosteroids among related toxicity toxicity occurs with renal dysfunction. The
dose therefore needs to be carefully adjusted
patients with IRIS. according to the estimated glomerular
filtration rate
Monitoring of patients • Days 0, 3 and 7: creatinine and potassium (and
Immunological failure on antiretroviral treatment receiving amphotericin B magnesium, if available)
and flucytosine • Days 0 and 7: full blood count (with a differential
If patients with priorly treated CM develop immunological count if available). Day 3: full blood count and
failure on ART and their CD4 count drops below 200 cells/µL differential can be considered when flucytosine is
used, especially if baseline abnormalities exist.
after secondary prophylaxis has been stopped, the panel Flucytosine may cause bone marrow suppression
but this is uncommonly observed with short
advises restarting fluconazole at 200 mg daily. This may be duration of use and the current suggested dosing
schedule
considered for patients with priorly treated cryptococcal • Fluid input and output monitoring
antigenaemia too. Refer to the Maintenance phase (secondary Management of • Refer to Recommendation 3 (baseline renal
impairment section)
prophylaxis) for duration of treatment. amphotericin B-related • Febrile reactions can be treated with paracetamol
toxicities
1 g 30 min before infusion (if severe,
hydrocortisone 25 mg IV can be given before
Non-adherence to maintenance treatment subsequent infusions)
Management of flucytosine- • If grade 4 neutropenia or if any neutropenia-
Among patients who stop taking fluconazole maintenance related toxicities related complications develop, reduce the
prematurely and then return for care but are asymptomatic, flucytosine dose and repeat a neutrophil
count immediately. If neutropenia is confirmed,
the panel advises simply restarting fluconazole 200 mg stop the flucytosine and switch to fluconazole.
If the patient was being treated with
daily and monitoring closely for recurrence of meningitis. amphotericin B and flucytosine, consider
Symptomatic patients should be fully investigated a second week of amphotericin B deoxycholate
treatment.
for CM. Community adherence support for ART †, For adolescents and children, doses should be calculated by body weight; ‡, For children
and fluconazole should be arranged. Refer to the 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
Maintenance phase (secondary prophylaxis) for duration to amphotericin B administration. If saline is unavailable, then other parenteral rehydration
of treatment. solutions, for example, Darrow’s solution or Ringer’s lactate, that already contain potassium
can be used.
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