Swissmedic Vigilance News Edition 21 – November 2018

In order to highlight the risk of confusion,
the Swiss Information for healthcare professionals
for Fungizone ® already contains the
following warnings:
"Multiple parenteral forms of the active substance
amphotericin B exist. Please check the
preparation name and dosage before use.
Caution during Fungizone dosing: Under no
circumstances should a total daily dose of 1.5
mg/kg body weight be exceeded. An overdose
can result in potentially fatal cardiac or
respiratory arrest."
In view of the higher permitted dosage of
AmBisome ® , the problem of overdose arises
when Fungizone ® is administered at the Am-
Bisome ® dosage. By contrast, using AmBisome
® instead of Fungizone ® can lead to underdosage.
The product information for Am-
Bisome ® explicitly refers to this in the dosage
section:
"Since the dosage of AmBisome is productspecific
it may NOT be applied to other medicines
containing amphotericin B."
Case reports
The product information texts and packaging
elements of Fungizone ® and AmBisome ®
already include sufficient references to the
risk of confusion and the associated risk of
overdose. Nevertheless, there are two
known cases in Switzerland where the dosage
recommendations for liposomal amphotericin
B were applied to the administration
of non-liposomal amphotericin B.
In 2015, a 39-year-old woman received an
overdose with non-liposomal amphotericin
B, resulting in multiple life-threatening
events (ventricular tachycardia, cardiac arrest,
hyperkalaemia, acute kidney injury,
liver cell damage, haemolytic anaemia and
thrombocytopenia). By the time of the report,
the patient had recovered from the
cardiac arrest and hyperkalaemia, but not
from the acute liver damage, haemolytic
anaemia or thrombocytopenia.
In a case from Switzerland published in 2016,
an immunosuppressed 9-year-old boy recovering
from a bone marrow transplant suffered
diarrhoea, vomiting, acute renal failure,
fever and shivering as a result of an amphotericin
B overdose. The patient had been
given Fungizone ® instead of the prescribed
intravenous AmBisome ® . Consequently, the
patient had received ten times the recommended
dose. After rehospitalisation and
several weeks of treatment, the child recovered
completely (6).
Conclusion
The purpose of a Direct Healthcare Professional
Communication (DHPC), formerly
termed a Dear Doctor Letter (DDL), is to inform
health professionals about important,
newly identified drug risks – particularly if
these are unexpected – and corresponding
risk minimisation measures, with a view to
prompting a relevant change in approach. In
this case, the product information texts and
packaging elements for the drugs concerned
already contained sufficient references to
the risk of confusion and thus the associated
risk of overdose. The risk of confusion is
known in professional circles and published
in the literature. The information in these
texts should already have been taken into
account by the treating professionals. In this
specific case, Swissmedic is therefore not
sending out a DHPC, but would like to remind
professionals of the risk of mix-ups between
non-liposomal and liposomal parenteral
forms of amphotericin B. Since the dosage
of amphotericin B preparations is product-specific
it may not be applied to other
medicines containing amphotericin B. In
view of the parallel use of different amphotericin
B solutions in hospitals, measures
should be taken to make it impossible, or at
least more difficult, to confuse these preparations.
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