Page 23 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 10 of 16 Guideline

Background amphotericin B deoxycholate powder from each 50 mg vial
should be aseptically reconstituted in 10 mL of sterile water.
Amphotericin B deoxycholate-related toxicities
The calculated volume of the concentrate (i.e. reconstituted
Major adverse effects of amphotericin B deoxycholate include drug in sterile water) should be injected into a 1 L bag of 5%
acute kidney injury (AKI) (caused by renal vasoconstriction dextrose water and shaken to mix well. Amphotericin B
and acute tubular necrosis) usually in the second week of deoxycholate should never be mixed with normal saline or
therapy, hypokalaemia, hypomagnesaemia, anaemia, febrile half-normal saline as it will precipitate. Once mixed, the
reactions and chemical phlebitis. Acute kidney injury and solution, containing ≤ 0.1 mg of amphotericin B per 1 mL of
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electrolyte abnormalities may be prevented by pre-hydration, 5% dextrose water for infusion through a peripheral
by avoiding concurrent use of other nephrotoxins (e.g. intravenous line, must be infused within 24 h of preparation,
NSAIDs and aminoglycosides) and by routine administration or else it should be discarded. A test dose is not recommended
55
of potassium and magnesium supplements. Phlebitis is very and protection of the solution from light with a brown bag is
common among patients receiving amphotericin B and unnecessary. The line that is used for amphotericin B
55
increases the risk of localised cellulitis as well as sepsis. infusion should not be used to simultaneously administer
Anaemia commonly occurs among patients receiving other medications. The solution should be infused over 4 h or
amphotericin B and can be clinically significant particularly more (infusion < 4 h can result in cardiac complications).
among those with a low baseline haemoglobin level. Decreases Once the infusion is complete, the line should be flushed
in haemoglobin of greater than 2 g/dL occurred in 50% – 71% immediately with normal saline.
of patients over 2 weeks’ treatment in an individual-level
analysis of data from several trials. It is important to also
49
exclude other treatable causes of anaemia and consider Flucytosine: Flucytosine (500 mg tablets) should be stored
below 25 °C in a cool, dry area. With normal renal function,
transfusion among symptomatic patients. It should be noted the total daily dose is 100 mg/kg/day given in four divided
that both the nephrotoxic effect of amphotericin B deoxycholate doses (i.e. every 6 h) per os (Table 5). Nausea and vomiting
and the decrease in haemoglobin are less commonly observed may occur and can be attenuated by administering flucytosine
when using the preferred regimen of 1-week amphotericin B tablets individually during a 15-min window or by pre-
combined with flucytosine compared to regimens using 2 medication with anti-emetics.
weeks of amphotericin B (Table 7). 8
Flucytosine-related toxicities Prevention of toxicities
Flucytosine is associated with bone marrow toxicity and Amphotericin B deoxycholate
resultant anaemia, neutropenia and thrombocytopenia. This Patients should be pre-hydrated with 1 L of normal saline
was observed particularly in early studies when flucytosine containing 1 ampoule of potassium chloride (20 mmol K per
+
was used at high doses for prolonged periods of time. 50,51,52 10 mL ampoule) infused over 2 h before administration of
The reported prevalence of toxicity from recent trials, using amphotericin B deoxycholate. This reduces renal toxicity and
lower doses for shorter periods, has been much lower. In the hypokalaemia. Patients should be given 1200 mg potassium
ACTA trial, the preferred regimen of 1-week amphotericin B chloride orally twice daily (equivalent to 16 mmol of oral
combined with flucytosine 100 mg/kg/day was not potassium, e.g. two Slow-K 600 mg tablets twice daily, 8 mmol
associated with an increase in severe neutropenia compared +
to flucytosine-free regimens. The bioavailability of oral K per tablet) and up to 1500 mg magnesium chloride orally
8
daily (e.g. two Slow-Mag 535 mg tablets daily, 5.33 mmol
flucytosine was reduced among Thai patients with advanced Mg2+ per tablet, or two Ultimag tablets daily, 660 mg Mg2+
HIV disease compared to the intravenous formulation, with zinc oxide 6 mg) for the duration of treatment with
minimising toxicity but with no demonstrated difference in amphotericin B deoxycholate. Routine pre-emptive potassium
26
early fungicidal activity. For these reasons, therapeutic
53
monitoring of serum levels is not recommended in the setting supplementation should not be given to patients with pre-
of HIV-related CM. Flucytosine plasma clearance is closely existing renal impairment or hyperkalaemia. To minimise the
risk of phlebitis, lines should be flushed with normal saline
related to creatinine clearance and flucytosine thus immediately after amphotericin B infusion is complete. The
accumulates with impaired renal function; this may lead to empty bag should not be left attached to the intravenous line.
increased risk of toxicity. Close monitoring of renal function
and appropriate dose adjustment according to estimated The intravenous line should be removed if the patient develops
creatinine clearance are therefore essential. 54 a fever after the infusion or at the first sign of redness or
discomfort at the insertion site. Febrile reactions may occur; in
order to prevent recurrence, the infusion should be administered
Detailed recommendations at a slow rate over the first half hour while observing the patient
Administration closely and treatment such as paracetamol may be required.
Amphotericin B deoxycholate: Amphotericin B deoxycholate
powder (50 mg vials) should be refrigerated between 2 °C Flucytosine
and 8 °C and protected from light. The total daily dose of Renal function should be closely monitored especially when
55
amphotericin B is calculated based on a dose of 1 mg/kg/day; flucytosine is combined with amphotericin B deoxycholate.

http://www.sajhivmed.org.za 16 Open Access